Erratum: [Corrigendum] Mesenchymal stem cells expressing interleukin­18 inhibit breast cancer in a mouse model.

[This corrects the article DOI: 10.3892/ol.2018.8166.].

Erratum: [Corrigendum] Mesenchymal stem cells expressing interleukin­18 suppress breast cancer cells in vitro.

[This corrects the article DOI: 10.3892/etm.2015.2286.].

[Retracted] TGF­ß1 induces peritoneal fibrosis by activating the Smad2 pathway in mesothelial cells and promotes peritoneal carcinomatosis.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the fluorescence microscopy data shown in Fig. 6A and B were strikingly similar to data appearing in different form in Fig. 7 in a previously published paper [Lv Z­D, Na D, Liu F­N, Du Z­M, Sun Z, Li Z, Ma X­Y, Wang Z­N and Xu H­M: Induction of gastric cancer cell adhesion through transforming growth factor­beta1­mediated peritoneal fibrosis. J Exp Clin Cancer Res 29: 139, 2010], which featured some of the same authors, although the data were shown to portray results obtained under different experimental conditions. Furthermore, the data in Fig. 7A for the 'TGF­ß1' and the 'TGF­ß1 + siRNAcon' experiments contained an overlapping section, such that these data appeared to have been derived from the same original source, even though they were intended to show the results from differently performed experiments. Owing to the fact that the contentious data in the above article had already been published prior to its submission to International Journal of Molecular Medicine, and due to a lack of overall confidence in the presented data, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 29: 373­379, 2012; DOI: 10.3892/ijmm.2011.852].

Paired­related homeobox 1 overexpression promotes multidrug resistance via PTEN/PI3K/AKT signaling in MCF­7 breast cancer cells.

Multidrug resistance (MDR) is a major cause of disease relapse and mortality in breast cancer. Paired­related homeobox 1 (PRRX1) is associated with the epithelial­mesenchymal transition (EMT), which is involved in tumor development, including cell invasion and MDR. However, the effect of PRRX1 on MDR had not clearly established. The present study investigated the influence of PRRX1 on MDR and the underlying molecular mechanisms in MCF­7 breast cancer cells. MCF­7 cells were divided into PRRX1+ group (cells transfected with a recombinant plasmid carrying the PRRX1 gene), negative control group (cells transfected with a blank vector) and blank group (untreated cells). It was found that the relative protein and mRNA expression levels of PRRX1, N­cadherin, vimentin and P­glycoprotein were significantly higher in PRRX1­overexpressing MCF­7 cells compared with those in control cells. The half­maximal inhibitory concentration of three groups after treatment with docetaxel and cis­platinum complexes were significantly higher in PRRX1­overexpressing MCF­7 cells compared with those in control cells. Furthermore, relative PTEN expression decreased significantly and levels of phosphorylated PI3K and AKT increased substantially in PRRX1­overexpressing MCF­7 cells. These results indicated that PRRX1 overexpression may induce MDR via PTEN/PI3K/AKT signaling in breast cancer. It is highly recommended that PRRX1 gene expression detection should be performed in patients with breast cancer to aid the selection of more appropriate treatments, which will lead to an improved prognosis in clinical practice.

A randomized multicenter phase II trial of mecapegfilgrastim single administration versus granulocyte colony-stimulating growth factor on treating chemotherapy-induced neutropenia in breast cancer patients.

BACKGROUND: This study aimed to evaluate the efficacy and safety of mecapegfilgrastim (HHPG-19K) with different doses compared to granulocyte colony-stimulating growth factor (G-CSF) in treating chemotherapy-induced neutropenia in breast cancer patients. METHODS: A total of 182 breast cancer patients were enrolled in this multi-center, randomized, phase II trial and developed neutropenia after first cycle chemotherapy. Patients were then assigned as 1:1:1 ratio to receive 100 µg/kg HHPG-19K single injection (HHPG-19K-N group), 150 µg/kg HHPG-19Ksingle injection (HHPG-19K-H group) and 5 µg/kg G-CSF daily injection (G-CSF group) at day 3 of the second cycle (cycle 2) chemotherapy. The primary endpoint was incidence of grade ≥3 neutropenia during cycle 2. Study drug-related adverse events during cycle 2 were recorded for safety assessment. RESULTS: During cycle 2 chemotherapy, both HHPG-19K-N and HHPG-19K-H groups exhibited lower incidence of grade ≥3 neutropenia compared with G-CSF group, while no difference was observed between HHPG-19K-N and HHPG-19K-H groups. Also, better outcomes were observed in HHPG-19K-N and HHPG-19K-H groups compared with G-CSF group regarding to grade 4 neutropenia, duration of grade ≥3 neutropenia, duration of grade 4 neutropenia, incidence of febrile neutropenia (FN) and rescue application of G-CSF, time to ANC recovery, while no difference of these outcomes between HHPG-19K-N and HHPG-19K-H groups was observed. For safety analysis, the incidences of hematologic and non-hematologic adverse events were similar among the 3 groups. CONCLUSIONS: HHPG-19K presents with better clinical efficacy as well as equal tolerance compared with G-CSF in treating chemotherapy-induced neutropenia in breast cancer patients.

miR-135b promotes proliferation and metastasis by targeting APC in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. The aim of our study was to investigate the functional role of microRNA-135b (miR-135b) in TNBC. A real-time polymerase chain reaction assay was used to quantify miR-135b expression levels in 90 paired TNBC tissue and adjacent normal tissue samples. Wound-healing and transwell assays were performed to evaluate the effects of miR-135b expression on the migration and invasion of TNBC cells. Luciferase reporter and western blot analyses were used to verify whether the mRNA encoding APC is a major target of miR-135b. In the current study, we found that miR-135b was highly expressed in TNBC tissue and cells, and the expression levels were correlated with lymph node status and TNM stage. In TNBC cells, the ectopic expression of miR-135b promoted cell proliferation and invasion in vitro. In addition, our study proved that the overexpression of miR-135b significantly suppressed APC expression by targeting the 3'-untranslated region of APC, whereas enhanced APC expression could partially abrogate the miR-135b-mediated promotion of carcinogenic traits in TNBC cells. Taken together, our study demonstrated that miR-135b expression promoted the proliferation and invasion of TNBC by downregulating APC expression, indicating that miR-135b may serve as a promising target for the treatment of TNBC patients.

p53-independent role of MYC mutant T58A in the proliferation and apoptosis of breast cancer cells.

Myc proto-oncogene (MYC) is an oncoprotein that promotes proliferation and apoptosis. MYC mutations frequently disrupt the apoptotic processes during tumorigenesis. In the present study, the effects of the MYC point mutation T58A on the progression of a cellular tumor antigen p53 (p53)-/- human breast cancer cell line was analyzed, and the mechanism of p53-independent MYC-induced apoptosis was investigated. HCC1937 cells were transfected with mutant (T58A) or wild-type (WT) MYC using lentiviral vectors. The proliferation of transfected cells was evaluated by colony formation and MTT assays, and apoptosis was analyzed by flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assays. WT MYC was transfected into HCC1937 cells exhibiting p14/p21 silencing through lentivirus-mediated RNA interference. The expression levels of Bim were detected by reverse transcription-quantitative polymerase chain reaction and western blot analyses. Mutant MYC proteins retained the ability to stimulate the proliferation of HCC1937 cells, although they were defective at promoting apoptosis due to a failure to induce the Bcl-2 homology 3 domain-only protein Bim. When p14 was silenced, the effects of mutant MYC on proliferation and apoptosis were weakened. When p21 was silenced, the effects of mutant MYC were strengthened. Breast cancer-derived T58A MYC mutations are unable to activate Bim due to their failure to regulate p14/p21. It was concluded that mutant MYC was more effective compared with WT MYC at promoting the progression of breast cancer.

Mesenchymal stem cells expressing interleukin-18 inhibit breast cancer in a mouse model.

Development of an improved breast cancer therapy has been an elusive goal of cancer gene therapy for a long period of time. Human mesenchymal stem cells derived from umbilical cord (hUMSCs) genetically modified with the interleukin (IL)-18 gene (hUMSCs/IL-18) were previously demonstrated to be able to suppress the proliferation, migration and invasion of breast cancer cells in vitro. In the present study, the effect of hUMSCs/IL-18 on breast cancer in a mouse model was investigated. A total of 128 mice were divided into 2 studies (the early-effect study and the late-effect study), with 4 groups in each, including the PBS-, hUMSC-, hUMSC/vector- and hUMSC/IL-18-treated groups. All treatments were injected along with 200 µl PBS. Following therapy, the tumor size, histological examination, and expression of lymphocytes, Ki-67, cluster of differentiation 31 and cytokines [interleukin (IL)-18, IL-12, interferon (IFN)-γ and TNF-α] in each group were analyzed. Proliferation of cells (assessed by measuring tumor size and Ki-67 expression) and metastasis, (by determining pulmonary and hepatic metastasis) of breast cancer cells in the hUMSC/IL-18 group were significantly decreased compared with all other groups. hUMSCs/IL-18 suppressed tumor cell proliferation by activating immunocytes and immune cytokines, decreasing the proliferation index of proliferation marker protein Ki-67 of tumor cells and inhibiting tumor angiogenesis. Furthermore, hUMSCs/IL-18 were able to induce a more marked and improved therapeutic effect in the tumor sites, particularly in early tumors. The results of the present study indicate that hUMSCs/IL-18 were able to inhibit the proliferation and metastasis of breast cancer cells in vivo, possibly leading to an approach for a novel antitumor therapy in breast cancer.

PRRX1 drives tamoxifen therapy resistance through induction of epithelial-mesenchymal transition in MCF-7 breast cancer cells.

PURPOSE: Resistance to endocrine therapies is a major cause of disease relapse and mortality in estrogen receptor (ER)-positive breast cancers, which has been associated with tumor epithelial-mesenchymal transition (EMT). In this study, we investigated the contribution of the EMT-inducing factor paired related homeobox 1 (PRRX1) to tamoxifen (TAM) resistance acquired in vitro using ER-positive MCF-7 breast cancer cells. METHODS: PRRX1 was overexpressed in MCF-7 cells through transfection; cells transfected with a blank vector served as the control. The morphological changes and transfection efficiency were observed by inverted fluorescence microscopy. The expression of ER and EMT-related proteins and genes was evaluated by Western blot and real-time polymerase chain reaction analysis, respectively. Finally, we evaluated the EMT features of the breast cancer cells and their response to TAM treatment. RESULTS: The transfection efficiency was greater than 80%, and the expression level of PRRX1 protein was significantly higher after transfection, whereas the expression of ER protein was significantly lower after transfection. The overexpression of PRRX1 changed the morphology of breast cancer cells from a "paving stone" to a long spindle shape. The mRNA expression levels of PRRX1 and vimentin were significantly higher, whereas that of E-cadherin was significantly lower after transfection. The proliferative level of the breast cancer cells after transfection was significantly increased at 12, 24 and 48 h after treatment with TAM. At 24 h of TAM treatment, the half-maximal inhibitory concentration of the transfected cells was significantly higher than that before transfection. Moreover, the PRRX1-overexpressing MCF-7 breast cancer cells acquired an EMT phenotype and displayed decreased levels of ER targets to ultimately acquire resistance to TAM. CONCLUSIONS: PRRX1 overexpression can induce EMT to promote resistance to TAM in MCF-7 breast cancer cells, partly by reducing ER expression. It is suggested that in clinical practice, PRRX1 gene expression detection can be performed in patients with hormone-receptor-positive breast cancer to guide our medication and prognosis.

MiR-212-5p Suppresses the Epithelial-Mesenchymal Transition in Triple-Negative Breast Cancer by Targeting Prrx2.

BACKGROUND/AIMS: Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. Our study investigated the functional role of miR-212-5p in TNBC. METHODS: Realtime PCR was used to quantify miR-212-5p expression levels in 30 paired TNBC samples and adjacent normal tissues. Wound healing and Transwell assays were used to evaluate the effects of miR-212-5p expression on the invasiveness of TNBC cells. Luciferase reporter and Western blot assays were used to verify whether the mRNA encoding Prrx2 is a major target of miR-212-5p. RESULTS: MiR-212-5p was downregulated in TNBC, and its expression levels were related to tumor size, lymph node status and vascular invasion in breast cancer. We also observed that the miR-212-5p expression level was significantly correlated with a better prognosis in TNBC. Ectopic expression of miR-212-5p induced upregulation of E-cadherin expression and downregulation of vimentin expression. The expression of miR212-5p also suppressed the migration and invasion capacity of mesenchymal-like cancer cells accompanied by a morphological shift towards the epithelial phenotype. Moreover, our study observed that miR-212-5p overexpression significantly suppressed Prrx2 by targeting its 3'-untranslated region (3'-UTR) region, and Prrx2 overexpression partially abrogated miR-212-5p-mediated suppression. CONCLUSIONS: Our study demonstrated that miR-212-5p inhibits TNBC from acquiring the EMT phenotype by downregulating Prrx2, thereby inhibiting cell migration and invasion during cancer progression.

Silencing of Prrx2 Inhibits the Invasion and Metastasis of Breast Cancer both In Vitro and In Vivo by Reversing Epithelial-Mesenchymal Transition.

BACKGROUND/AIMS: Epithelial-mesenchymal transition (EMT) is recognized as a crucial mechanism in breast cancer progression and metastasis. Paired-related homeobox 2 (Prrx2) has been identified as a new EMT inducer in cancer, but the underlying mechanisms are still poorly understood. METHODS: The expression of Prrx2 was assessed by immunohistochemistry in breast cancer tissues to evaluate the clinicopathological significance of Prrx2, as well as the correlation between Prrx2 and EMT. Short hairpin RNA knockdown of Prrx2 was used to examine cellular effects of Prrx2, detecte the expression of Wnt/ß-catenin signaling and EMT-associated proteins, and observe cell proliferation, invasion and migration abilities in vitro and in vivo. RESULTS: Clinical association studies showed that Prrx2 expression was related to tumor size, lymph node metastasis, tumor node metastasis stages, EMT and poor survival. Results also showed that knockdown of Prrx2 could alter cell morphology, suppressed the abilities of cell proliferation, invasion and migration in breast cancer. Moreover, silencing of Prrx2 induced the mesenchymal-epithelial transition and prevented nuclear translocation of ß-catenin, inhibited wnt/ß-catenin signaling pathway. CONCLUSION: Our study indicated that Prrx2 may be an important activator of EMT in human breast cancer and it can serve as a molecular target of therapeutic interventions for breast cancer.

Silencing of Prrx1b suppresses cellular proliferation, migration, invasion and epithelial-mesenchymal transition in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a highly aggressive tumour subtype associated with poor prognosis. The mechanisms involved in TNBC progression remains largely unknown. To date, there are no effective therapeutic targets for this tumour subtype. Paired-related homeobox 1b (Prrx1b), one of major isoforms of Prrx1, has been identified as a new epithelial-mesenchymal transition (EMT) inducer. However, the function of Prrx1b in TNBC has not been elucidated. In this study, we found that Prrx1b was significantly up-regulated in TNBC and associated with tumour size and vascular invasion of breast cancer. Silencing of Prrx1b suppressed the proliferation, migration and invasion of basal-like cancer cells. Moreover, silencing of Prrx1b prevented Wnt/ß-catenin signaling pathway and induced the mesenchymal-epithelial transition (MET). Taken together, our data indicated that Prrx1b may be an important regulator of EMT in TNBC cells and a new therapeutic target for interventions against TNBC invasion and metastasis.

miR-655 suppresses epithelial-to-mesenchymal transition by targeting Prrx1 in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype that lacks effective targeted therapies. The epithelial-to-mesenchymal transition (EMT) is a key contributor in the metastatic process. In this study, we found that miR-655 was down-regulated in TNBC, and its expression levels were associated with molecular-based classification and lymph node metastasis in breast cancer. These findings led us to hypothesize that miR-655 overexpression may inhibit EMT and its associated traits of TNBC. Ectopic expression of miR-655 not only induced the up-regulation of cytokeratin and decreased vimentin expression but also suppressed migration and invasion of mesenchymal-like cancer cells accompanied by a morphological shift towards the epithelial phenotype. In addition, we found that miR-655 was negatively correlated with Prrx1 in cell lines and clinical samples. Overexpression of miR-655 significantly suppressed Prrx1, as demonstrated by Prrx1 3'-untranslated region luciferase report assay. Our study demonstrated that miR-655 inhibits the acquisition of the EMT phenotype in TNBC by down-regulating Prrx1, thereby inhibiting cell migration and invasion during cancer progression.

[Effect of miRNA-135b on proliferation, invasion and migration of triple-negative breast cancer by targeting APC].

OBJECTIVE: To explore the expression of miRNA-135b in a variety of breast cancer cell lines and its function on the proliferation, invasion and migration in triple-negative breast cancer cell lines by targeting adenomatous polyposis coli (APC). METHODS: Quantitative real-time (RT)--PCR was used to detect the expression of miRNA-135b in seven breast cancer cell lines and one normal breast cell line. The three-negative breast cancer cell lines MDA-MB-231 and MDA-MB-468 with miRNA-135b high-expression were divided into three groups: the normal growth group, the negative control group (transfected with negative counter-part) and the experimental group (transfected with miRNA-135b inhibitors). RT- PCR and Western blot were used to explore the expression of APC. The proliferation was detected by Cell Counting Kit-8 (CCK-8) method and the invasion and migration were detected by Transwell method. RESULTS: The levels of miRNA-135b were higher in triple-negative breast cancer cell lines than other types, especially MDA-MB-231 (P=0.001) and MDA-MB-468 (P=0.036). Compared with normal growth group and negative control group, the mRNA and protein of APC were up-regulated in experimental group MDA-MB-231 (P=0.013, P=0.021), MDA-MB-468 (P=0.017, P=0.014). CCK-8 results showed that the proliferation rate of experimental group was decreased compared with negative control and normal growth group MDA-MB-231 (P=0.00 ), MDA-MB-468 (P=0.01). The invasion and migration ability of MDA-MB-231 (P=0.002, P=0.00) and MDA-MB-468 (P=0.01, P=0.00) were obviously decreased after transfected miRNA-135b inhibitors. CONCLUSION: The expressions of miRNA-135b were higher in most triple-negative breast cancer cell lines than others. miRNA-135b could promote the proliferation, invasion and migration in triple-negative breast cancer cell lines MDA-MB-231 and MDA-MB-468, and APC was one of the target genes of miRNA- 135b by participating in the process of regulation.

NKD1 down-regulation is associated with poor prognosis in breast invasive ductal carcinoma.

As a negative modulator of the canonical Wnt signaling pathway, Naked1 (NKD1) is widely expressed in many normal tissues. However, the expression and clinicopathological significance of NKD1 in patients with breast cancer is still unclear. The aim of this study was to evaluate NKD1 expression in breast cancer and to investigate the question of whether reduced expression of NKD1 may have any pathological significance in breast cancer development or progression. In this study, we performed western blotting and immunohistochemistry to evaluate the expression of NKD1 and relevance with clinicopathological factors in the breast invasive ductal carcinoma. Reduction of NKD1 was significantly correlated with lymph node metastasis, histological grade and ER expression in breast cancer. Patients with negative NKD1 expression had significantly lower cumulative postoperative 5 year survival rate than those with positive NKD1 expression. This interpretation is in keeping with the results obtained from our in vitro experiments on MDA-MB-231 cells, we demonstrated that upregulation of NKD1 expression by infect with an adenovirus containing a NKD1 vector significantly reduced the migration of breast cancer cells. These data suggest that NKD1 plays an important role in invasion in human breast cancer and it appears to be a potential prognostic marker for patients with breast cancer.

Mesenchymal stem cells expressing interleukin-18 suppress breast cancer cells in vitro.

Breast cancer is the most common malignancy among females throughout the world. Current treatments have unsatisfactory outcomes due to the dispersed nature of certain types of the disease. The development of a more effective therapy for breast cancer has long been one of the most elusive goals of cancer gene therapy. In the present study, human mesenchymal stem cells derived from umbilical cord (hUMSCs) genetically modified with interleukin 18 (IL-18) gene were used to study the effect of hUMSCs/IL-18 on the growth, migration and invasion of MCF-7 and HCC1937 cells in vitro. The hUMSCs could be efficiently modified by lentiviral systems and stably expressed IL-18 protein. hUMSCs/IL-18, but not hUMSCs without the IL-18 gene transduction, significantly suppressed the proliferation, migration and invasion of the MCF-7 and HCC1937 cells. The mechanism of this proliferation suppression may have involved the induction of G1- to S-phase arrest of the breast cancer cells by the hUMSCs/IL-18. In conclusion, hUMSCs/IL-18 can suppress the proliferation, migration and invasion of breast cancer cells in vitro and may provide an approach for a novel antitumor therapy in breast cancer.

[Role of transforming growth factor-ß1 in epithelial-mesenchymal transition of mesothelial cells and its effect on peritoneal metastasis of gastric cancer].

OBJECTIVE: To elucidate the role of transforming growth factor-beta1(TGF-ß1) in epithelial-mesenchymal transition of mesothelial cells and peritoneal metastasis of gastric cancer. METHODS: HMrSV5 cells, a human peritoneal mesothelial cell line, were incubated with TGF-ß1, and their morphological changes were observed by phase contrast microscopy. Expressions of α-smooth muscle actin (α-SMA), vimentin, cytokeratin, E-cadherin, phosphorylated-Smad2 and Smad2 were examined by Western blotting. After fibroblastic-like mesothelial cells were co-incubate with HSC-39 cells(gastric cancer cell line), the adhesion and invasion potential of HSC-39 were evaluated by adhesion and invasion assay in vitro. RESULTS: Few mesothelial cells converted to spindle fibroblast-like morphology for 24 h, and remarkable phenotypic changes were observed at 72 h of TGF-ß1 activation. TGF-ß1 could induce α-SMA and vimentin expression, and down-regulate cytokeratin and E-cadherin expression in mesothelial cells (P<0.05). TGF-ß1 induced phosphorylation of Smad2 within 15 min of stimulation, reached a maximum at 30 min after treatment and remained high level during the experiment without affecting total Smad2 expression(P>0.05). The percentage of HSC-39 gastric cancer cells adhered were significantly increased as compared to the control. When the mesothelial cells were treated by TGF-ß1 for 72 h, the increased adhesion percentage was(146±17)%(P<0.05). After fibroblastic-like mesothelial cells co-incubated with HSC-39 cells for 48 h, more cancer cells [(61.1±11.4) cells/view field] invaded the coated membrane as compared to the control group [(31.9±8.1) cells/view field] (P<0.05). CONCLUSION: TGF-ß1 can induce the transition of mesothelial cells into myofibroblasts and Smad2 signal pathway may play a role in this transition, which is associated with increased adhesion and invasiveness of gastric cancer cells, and provides favorable environment for the dissemination of gastric cancer.

CXCL12 chemokine expression suppresses human breast cancer growth and metastasis in vitro and in vivo.

Chemokine receptors are now known to play an important role in cancer growth and metastasis. However, there is little information regarding chemokine expression in breast cancer. The aim of this study was to evaluate CXCL12 expression in breast cancer and to investigate the question of whether reduced expression of CXCL12 may have any pathological significance in breast cancer development or progression. In this study, we performed western blotting and immunohistochemistry to evaluate the expression of CXCL12 and relevance with clinicopathological factors in the invasive ductal carcinoma. Reduction of CXCL12 was significantly correlated with tumor size, lymph node metastasis, TNM stage and Her-2 expression in breast cancer. Patients with negative CXCL12 expression had significantly lower cumulative postoperative 5 year survival rate than those with positive CXCL12 expression. In addition, we demonstrated that upregulation of CXCL12 expression by infection with an adenovirus containing a CXCL12 vector significantly inhibited cell growth and reduced the migration of breast cancer cells. Furthermore, animal studies revealed that nude mice injected with the Ad-CXCL12 cell lines featured a lighter weight than the control cell lines. These data suggest that CXCL12 plays an important role in cell growth and invasion in human breast cancer and it appears to be a potential prognostic marker for patients with breast cancer.

[Effect of interleukin-18 gene modified human umbilical cord mesenchymal stem cells on proliferation of breast cancer cell].

OBJECTIVE: To establish human umbilical cord mesenchymal stem cells (HUMSCs) strain transfected with interleukin-18 (IL-18) gene and examine its effects on the proliferation of breast cancer cell (MCF-7). METHODS: HUMSCs were isolated and cultured. And the lentivirus-IL-18 vector containing human IL-18 gene was constructed and transfected into HUMSCs. The expressions of IL-18 gene mRNA and protein were detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. After co-culturing for 1, 3, 5 days, Transwell and cell counting kit-8 (CCK-8) assays were performed on MCF-7 to plot the cell growth curve. RESULTS: IL-18-HUMSCs could stably express of IL-18 gene and inhibit the proliferation of breast cancer cells. The IL-18 mRNA relative expression amounts were 1.40 ± 0.21 for experimental group (IL-18-HUMSCs), 0.59 ± 0.09 for negative control group (NV-HUMSCs) and 0.71 ± 0.05 for blank control group (HUMSCs). As compared with control group, the difference was statistically significant (F = 31.81, P = 0.001). The relative expressions of IL-18 protein were 1.54 ± 0.27 for experimental group (IL-18-HUMSCs), 0.57 ± 0.04 for negative control group (NV-HUMSCs) and 0.59 ± 0.23 for blank control group (HUMSCs). As compared with control group, the difference was statistically significant (F = 22.32, P = 0.002). After co-culturing for 5 days, the cellular proliferation was significantly inhibited. CONCLUSION: IL-18 gene has been successfully transfected into HUMSCs and has a stable expression. And IL-18-HUMSCs can effectively inhibit the proliferation of breast cancer cells in vitro.

Curcumin induces apoptosis in breast cancer cells and inhibits tumor growth in vitro and in vivo.

Curcumin has shown therapeutic and/or adjuvant therapeutic effects on the treatment of some patients with breast cancer. However, its mechanisms of action are largely unknown. This study was designed to investigate its antitumor effect and underlying mechanisms in human breast cancer MDA-MB-231 and MCF-7 cells. The MTT assay was used to evaluate cell viability, and flow cytometry, acridine orange staining and transmission electron microscopy were used to detect apoptosis for cultured cells. The protein expression in cells was evaluated by western blot analysis. Breast tumors were established by subcutaneous injection of MDA-MB-231 cells in nude BALB/c mice, and curcumin was administered to the mice. The size of tumors was monitored and the weight of tumors was examined. The exposure of breast cancer cells to curcumin resulted in growth inhibition and the induction of apoptosis in a dose-dependent manner. We also found that the expression of Bcl-2 protein decreased and the expression of Bax protein increased which lead to an increase of the Bax/Bcl-2 ratio. In mice bearing MDA-MB-231 xenograft tumors, administration of curcumin showed a significant decrease of tumor volumes and tumor weight compared with the control. Our results showed that curcumin exhibited antitumor effects in breast cancer cells with an induction of apoptosis.