Efficacy of probiotics in the treatment of oral mucositis in head and neck cancer patients: a systematic review and meta-analysis.

OBJECTIVES: To assess the effect of probiotics in oral mucositis induced by chemotherapy or radiotherapy on patients with head and neck cancer (HNC). METHODS: The PubMed, Embase, Cochrane Library, Clinical trials were screened from January 2010 to April 2024. Randomized clinical trials (RCTs) comparing the efficacy of probiotics in treatment of oral mucositis in HNC were eligible. Outcomes of interest were incidence of oral mucositis and severe oral mucositis. The PROSPERO registration number was 42022384685. The Cochrane risk-of-bias tool (RoB2) was used to assess methodological quality of studies and GRADE criteria (GRADEpro) was applied for rating the certainty of evidence. Meta-analysis was performed by using RevMan 5.4. RESULTS: A total of eight RCTs comprising 691 patients with HNC were included in this meta-analysis. Probiotics administration significantly reduced the incidence of SOM (RR = 0.60, 95%CI: 0.46-0.78, P = 0.0002). However, it showed no distinct advantage in reducing the overall incidence of oral mucositis (RR = 0.88, 95%CI: 0.76-1.02, P = 0.08). Subgroup analysis found more benefit for reducing SOM in multi-bacterial treated group (RR = 0.35, 95%CI: 0.17-0.73, P = 0.005) than mono-bacterial treated group (RR = 0.69, 95%CI: 0.58-0.82, P < 0.0001). In Addition, probiotics could reduce the incidence of SOM in nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (RR = 0.43, 95%CI: 0.26-0.70, P = 0.0006). CONCLUSION: Probiotics reduced the incidence of SOM caused by chemotherapy or radiotherapy for HNC. The multi-bacterial combination therapy was more efficacious than the mono-bacterial therapy. Moreover, probiotics also reduced the incidence of SOM in nasopharyngeal carcinoma. However, the advantage of probiotics had not been established in the overall incidence of OM.

Effect of aspirin on blood pressure in hypertensive patients: a systematic review and meta-analysis.

INTRODUCTION: Aspirin is widely used for secondary prevention in patients with hypertension. However, previous studies mainly focused on the preventive effects of aspirin, and there has been a lack of reliable evidence on whether taking aspirin affects blood pressure This study aimed to investigate whether aspirin would affect the blood pressure in patients with hypertension. METHODS: PubMed, Cochrane database, Embase, Scopus and Medline databases were searched until September 2023. For continuous variables (e.g., blood pressure reduction), the mean difference (MD) was selected as the effect magnitude indices. We used the Cochrane Collaboration's Risk of Bias tool to assess the risk of bias. RESULT: A total of five studies were included, comprising 20,312 patients. We found that aspirin did not affect SBP (MD = -0.78, 95% CI: - 2.41, 0.84). A similar result was found for DBP (MD = -0.86, 95% CI: - 2.14, 0.42). CONCLUSION: This study showed no significant difference in blood pressure between the aspirin and control groups, suggesting that aspirin does not affect blood pressure.

Effects of Pretreatment with Bifidobacterium bifidum Using 16S Ribosomal RNA Gene Sequencing in a Mouse Model of Acute Colitis Induced by Dextran Sulfate Sodium.

BACKGROUND Bifidobacterium is a potentially effective and safe treatment for patients with inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease. However, information on the influence of B. bifidum on gut microbial diversity of treated and pretreated IBD patients is limited. MATERIAL AND METHODS Our study investigated therapeutic and preventive effects of B. bifidum ATCC 29521 on C57BL/6 mice with dextran sulfate sodium (DSS)-induced acute colitis via 16S ribosomal ribonucleic acid (rRNA) gene sequencing. RESULTS Treatment and pretreatment of mice with B. bifidum ATCC 29521 significantly alleviated the severity of acute colitis on the basis of clinical and pathologic indicators. 16S rRNA gene sequencing showed that administration of B. bifidum shifted composition of the gut microbiome in mice with DSS-induced colitis in both treated and pretreated groups. Mice pretreated with B. bifidum ATCC 29521 for 21 days exhibited a significant increase in diversity of the gut microbiome. Principal coordinate analysis showed that gut microbiota structure was shaped by different treatments and time points. On the basis of linear discriminant analysis of effect size, the abundance of the genus Escherichia-Shigella, belonging to the family Enterobacteriaceae, was reduced in the B. bifidum-treated group, indicating that pathogens were inhibited by the B. bifidum treatment. Furthermore, the genera Intestinimonas and Bacteroides were significantly associated with the B. bifidum-pretreated group. CONCLUSIONS 16S rRNA gene sequencing showed that pretreatment with B. bifidum ATCC 29521 reduced intestinal inflammation and altered the gut microbiota to favor the genera Intestinimonas and Bacteroides.

Inhibition of Euchromatic Histone Lysine Methyltransferase 2 (EHMT2) Suppresses the Proliferation and Invasion of Cervical Cancer Cells.

EHMT2 (euchromatic histone lysine methyltransferase 2), a histone methyltransferase, has been shown to be involved in multiple human cancers. In this study, we determined mRNA and protein expression of EHMT2 in cervical cancer cells and normal cervical epithelial cells. EHMT2 was inhibited with short hairpin RNA (shEHMT2) in cervical cancer cells. Cell viability, colony proliferation, apoptosis, adhesion, and invasion assays and Western blot were performed to assess the function of EHMT2. As a result, EHMT2 was upregulated in human cervical cancer cells compared to normal cervical epithelial cells. Suppression of EHMT2 expression impairs cell proliferation and induces apoptosis. Furthermore, EHMT2 silencing inhibited cell adhesion and invasion. Finally, knockdown of EHMT2 resulted in a reduction of the expression of the tumorigenic proteins Bcl-2, Mcl-1, and Survivin and in an increase in the expression of the anti-malignant protein E-cadherin. In conclusion, our data suggest that EHMT2 plays a key role in cell proliferation and metastatic capacity in cervical cancer cells and could serve as a potential therapeutic target.

Actinomycosis presenting as a nasopharyngeal mass: A case report.

Actinomycetes are predominantly pathogenic bacteria that lack aerial hyphae and do not form spores. They are generally anaerobic or facultative anaerobic Gram-positive bacteria, belonging to the prokaryotic group. Actinomycetes are widely distributed in nature, similar to other bacteria, and are mostly saprophytic, with a few being parasitic. They are named as such due to their colony's radial form. The symptoms and signs of actinomycosis are atypical and rarely manifest in the nasopharynx. Consequently, it can be challenging to distinguish actinomycosis from nasopharyngeal carcinoma, making diagnosis difficult. Histopathology is usually relied upon for diagnosis, although culture may pose challenges. Fortunately, actinomycetes are highly sensitive to penicillin. Therefore, timely treatment with high doses of penicillin is crucial for successful recovery. In this case study, we present the details of a 53-year-old female patient with no history of mucosal damage or tooth decay but with a previous partial thyroidectomy. The patient experienced recurring neck pain accompanied by progressive limitation of neck movement. Nasopharyngoscopy revealed the presence of a smooth-surfaced mass. Subsequent biopsy, clinical imaging, microbiological analysis, and histological findings confirmed the diagnosis of actinomycosis.Following a comprehensive treatment plan involving a combination of penicillin and doxycycline for a duration of two months, the disease was successfully eradicated.

Development and internal validation of a nomogram based on peripheral blood inflammatory markers for predicting prognosis in nasopharyngeal carcinoma.

BACKGROUND: Inflammatory markers, including the product of neutrophil count, platelet count, and monocyte count divided by lymphocyte count (PIV) and the platelet-to-white blood cell ratio (PWR), have not been previously reported as prognostic factors in nasopharyngeal carcinoma (NPC) patients. In order to predict overall survival (OS) in NPC patients, our goal was to create and internally evaluate a nomogram based on inflammatory markers (PIV, PWR). METHODS: A retrospective study was done on patients who received an NPC diagnosis between January 2015 and December 2018. After identifying independent prognostic indicators linked to OS using Cox proportional hazards regression analysis, we created a nomogram with the factors we had chosen. RESULTS: A total of 630 NPC patients in all were split into training (n = 441) and validation sets (n = 189) after being enrolled in a population-based study in 2015-2018 and monitored for a median of 5.9 years. In the training set, the age, PIV, and PWR, selected as independent predictors for OS via multivariate Cox's regression model, were chosen to develop a nomogram. Both training and validation cohorts had C-indices of 0.850 (95% confidence interval [CI]: 0.768-0.849) and 0.851 (95% CI: 0.765-0.877). Furthermore, compared with traditional TNM staging, our nomogram demonstrated greater accuracy in predicting patient outcomes. The risk stratification model derived from our prediction model may facilitate personalized treatment strategies for NPC patients. CONCLUSION: Our findings confirmed the prognostic significance of the PWR and PIV in NPC. High PIV levels (>363.47) and low PWR (≤36.42) values are associated with worse OS in NPC patients.

AURKA, as a potential prognostic biomarker, regulates autophagy and immune infiltration in nasopharyngeal carcinoma.

BACKGROUND: Dysfunction of Aurora A (AURKA) plays crucial role in tumorigenesis and development of many types of cancer. However, the role of AURKA in nasopharyngeal carcinoma (NPC) has not been investigated yet. MATERIALS AND METHODS: Two independent NPC cohorts (GSE61218 and GSE102349) were enrolled from public database to investigate the expression level of AURKA between NPC and nasopharyngitis samples, the association of AURKA expression level with prognosis in NPC, and the potential mechanism of AURKA in NPC by using bioinformatics analyses. The expression level of AURKA protein in 62 paired NPC and nasopharyngitis tissues was evaluated by immunohistochemistry (IHC). Two NPC cell lines (SUNE-1 and CNE-2) were enrolled and the expression levels of AURKA in the NPC cells were inhibited by RNA interference. The expression levels of mRNAs were tested by qPCR and western-blotting. CCK-8 assay was applied to measure the cell growth. Cell migration was measured by using wound healing assays. RESULTS: AURKA was highly expressed in NPC samples compared to nasopharyngitis samples in GSE61218, which was confirmed by IHC. High expression of AURKA was associated with worse prognosis in GSE102349. Notably, silencing of AURKA was associated with significantly decreased cell growth and migration in NPC. Moreover, we found that the differentially expressed genes between high and low AURKA expression groups in GSE102349 were majorly enriched in both autophagy-related and immune-related pathways. Additionally, the expression level of AURKA was associated with the expression levels of autophagy-related genes and the infiltration of immune cells. CONCLUSION: AURKA overexpressed in NPC, which was associated with poor prognosis. Silencing of AURKA inhibited the proliferation and migration of NPC cells. Besides, AURKA might participate in the regulation of both autophagy and immunity in NPC.

Induction chemotherapy with sequential nimotuzumab plus concurrent chemoradiotherapy in advanced nasopharyngeal carcinoma: A retrospective real-world study.

Many locally advanced nasopharyngeal carcinoma patients develop local recurrence or distant metastasis. Our retrospective real-world study aims to evaluate the efficacy and safety of curative sequential approach with induction chemotherapy followed by concurrent chemoradiation + nimotuzumab as first-line therapy in advanced nasopharyngeal carcinoma. From 2015 to 2021, the clinic data of 117 patients with advanced nasopharyngeal carcinoma (stage III-IV a) who were treated in the Affiliated Hospital of Guangdong Medical University were retrospectively reviewed. Fifty-four patients in observation group received taxanes, cisplatin, and 5-fluorouracil/taxanes and cisplatin induction chemotherapy and nimotuzumab (200 mg, weekly) combined with concurrent chemo-radiotherapy (cisplatin: 40 mg/m2 weekly; intensity-modulated radiation therapy); 63 patients in control group received same therapy without nimotuzumab. There was no significant difference in patients' characteristic baseline between 2 groups (P > .05). The complete response rate and objective response rate of the observational group was significantly higher than control group (46.30% vs 17.64%, P = .01; 96.30% vs 82.54%, P = .02). The median follow-up time was 24.77 (3.53-65.97) months. Both of the median progress free survival time and overall survival time were not reached. The 5-year progression-free survival rate of observation group was greater than control group (84.40% vs 63.70%, hazard ratios 0.365, 95% confidence intervals 0.147-0.909, P = .03). The 5-year overall survival rate of observation group and control group were 91.70% and 84.60%, respectively (P = .20). None of the patients withdrew from the study due to adverse events. Nimotuzumab combined with concurrent chemoradiotherapy as first-line therapy in advanced nasopharyngeal carcinoma can improve objective response rate and 5-year progress free survival rate with good safety profile.

hsa_circ_0136839 regulates the malignant phenotypes of nasopharyngeal carcinoma via the Wnt/ß-catenin signaling pathway.

With the development of RNA sequencing (RNA-seq) technology, circular RNA (circRNA), a new class of RNA, has received much attention in cancer research. However, information available on the biogenesis and functional value of circRNAs in nasopharyngeal carcinoma (NPC) is scarce. In the present study, we screened the circRNA profile of the NPC cell line C666-1 compared with that of the normal control NP69 by RNA-seq and identified a novel and relatively higher expressed circRNA, hsa_circ_0136839. Hsa_circ_0136839 was markedly downregulated in NPC tissues, as confirmed by quantitative reverse transcription polymerase chain reaction. Functional in vitro studies revealed that hsa_circ_0136839 knockdown in C666-1 cell notably promoted cell proliferation, migration, and invasion abilities, as well as affected cell cycle distribution with an S-phase arrest. However, hsa_circ_0136839 overexpression in CNE2 cells resulted in an opposite response. Mechanistically, we demonstrated that aberrant hsa_circ_0136839 expression might affect the malignant phenotypes of NPC cells by activating the wnt/ß-catenin signaling pathway. Thus, our findings contribute to further the understanding of NPC pathogenesis and provide new ideas for NPC clinical diagnosis and treatment.

Cell Division Cycle-Associated Genes Are Potential Immune Regulators in Nasopharyngeal Carcinoma.

BACKGROUND: Cell division cycle-associated (CDCA) gene family is essential to cell cycle regulation. Numerous studies have illuminated that dysfunction of CDCA genes may not only lead to uncontrolled cell proliferation resulting in tumorigenesis but also influence immune cell infiltration in tumors. However, the role of the CDCA gene family on the prognosis and immune infiltration in nasopharyngeal carcinoma (NPC) remains to be unclear. METHODS: SBC human ceRNA array V1.0 was used to measure mRNA expression in three pairs of NPC tissues and nasopharyngitis tissues. The expression of CDCA8 was confirmed in an IHC microarray containing 130 NPC patients. Two external GEO cohorts were enrolled for further analysis. Prognosis analysis was performed using the Kaplan-Meier method. Gene set enrichment analysis (GSEA) was applied to explore the potential mechanism of CDCA genes in NPC. The relationship between CDCA gene family and immune infiltration in NPC was evaluated using the Xcell tool. RESULTS: CDCA genes were broadly upregulated in NPC tissues compared to nasopharyngitis tissues, and high expression of CDCA3/5/8 indicated worse prognosis in NPC. Besides cell cycle pathways, we found that CDCA3/5/8 were involved in multiple immune-related pathways. Overexpression of CDCA8 was strongly associated with less infiltration of CD8+ T cells and more infiltration of CD4+ Th1 cells and was negatively correlated with immune checkpoint blockade (ICB)-related genes. CONCLUSION: CDCA gene family was upregulated in NPC, and their expressions were associated with adverse prognosis. High expression of CDCA8 was associated not only with poor prognosis, but also with less immune infiltration and downregulation of ICB-related genes in NPC.

Circulating Tumor Cells and Fibronectin 1 in the Prognosis of Nasopharyngeal Carcinoma.

OBJECTIVE: Nasopharyngeal carcinoma is highly endemic in Southeast China. Circulating tumor cell is an important biomarker in the prognosis of variety kinds of cancers. Overexpression of fibronectin 1 was observed in variety kinds of malignancies and may contribute to progress and metastasis of the cancers. The current study was aimed to investigate phenotypes of circulating tumor cell in nasopharyngeal carcinoma blood and fibronectin 1 expression in the circulating tumor cell, and their clinical application in predicting nasopharyngeal carcinoma prognosis. METHODS: Blood samples were obtained from nasopharyngeal carcinoma patients before and after treatment. CanPatrol circulating tumor cell enrichment and RNA in situ hybridization were applied to identify circulating tumor cell and its phenotypes. Fibronectin 1 messenger RNA expression in the cells of circulating tumors was examined by messenger RNA-in situ hybridization. RESULTS: Circulating tumor cell was not associated with tumor characteristics or lymph node metastasis. Patients with >9 circulating tumor cells or >5 mesenchymal phenotype circulating tumor cell per 5-mL blood had poorer progression-free survival (P < .05). Multivariable analysis demonstrated that 2 or more mesenchymal phenotype circulating tumor cells with high fibronectin 1 messenger RNA expression predicted shorter progression-free survival (P < .05). CONCLUSIONS: Circulating tumor cells with high-level fibronectin 1 expression was associated with poor survival in patients with nasopharyngeal carcinoma and could be an independent prognostic factor for nasopharyngeal carcinoma.

Erastin decreases radioresistance of NSCLC cells partially by inducing GPX4-mediated ferroptosis.

The aim of the present study was to examine whether erastin influences radioresistance in non-small cell lung cancer (NSCLC) cells and produce a preliminary investigation into its mechanism of action. The radioresistant subtype of NSCLC cells, A549-R and H460-R, were induced by high-dose hypofractionated irradiation. Erastin was used to treat the radioresistant cells and radiosensitivity was examined by colony formation assays. Cell death was determined after the cells were treated with erastin, irradiation (IR) or erastin together with IR. The expression of glutathione peroxidase 4 (GPX4) expression in the parental cells and radioresistance cells was detected by western blotting. GPX4 expression in the radioresistance cells was subsequently inhibited, radiosensitivity and cell death was measured, and erastin enhanced radiosensitivity in A549-R and H460-R cells. Erastin and IR exhibited a combined effect on killing cells, as co-treatment with erastin and IR demonstrated a higher effect on killing cells compared with erastin or IR alone. GPX4 expression was inhibited by erastin in the radioresistant cells. Inhibiting GPX4 expression also radiosensitized NSCLC cells to radiation in the radioresistant cell lines. Erastin-induced and GPX4-inhibition-induced cell death could partially be rescued by deferoxamine, but not Z-VAD-FMK and olaparib, which indicated that erastin and GPX4-inhibition induced ferroptosis in the radioresistant cells. Erastin decreased radioresistance of NSCLC cells partially by inducing GPX4-mediated ferroptosis.

Niclosamide sensitizes nasopharyngeal carcinoma to radiation by downregulating Ku70/80 expression.

The aim of the present study was to investigate whether niclosamide could sensitize the nasopharyngeal carcinoma cells to radiation and further explore the underlying mechanisms. CCK-8 assay was used to determine the effect of niclosamide on the proliferation of NPC cells. Colony formation assay was used to evaluate the radiosensitizing effect of niclosamide on NPC cells. Flow cytometry analysis was used to determine the apoptosis of NPC cells induced by niclosamide. Immunofluorescent staining was used to detect the formation of γ-H2AX foci and the localization of Ku70/80 proteins in NPC cells. Real-time PCR quantification analysis was used to examine the level of Ku70/80 mRNA. DNA damage repair-related proteins were detected by western blot analysis. Our results showed that niclosamide markedly suppressed the proliferation of NPC cells. Niclosamide pretreatment followed by irradiation reduced the colony forming ability of NPC cells. Niclosamide in combination with irradiation significantly increased the apoptotic rate of NPC cells. Niclosamide significantly reduced the transcriptional level of K70/80 but not the translocation of Ku70/80 protein induced by irradiation. In conclusion, our study demonstrated that niclosamide could inhibit the growth of NPC cells and sensitize the NPC cells to radiation via suppressing the transcription of Ku70/80.

Niclosamide enhances the cytotoxic effect of cisplatin in cisplatin-resistant human lung cancer cells via suppression of lung resistance-related protein and c-myc.

Lung cancer is a leading cause of cancer-associated mortality worldwide. The cisplatin (DDP)­based chemotherapy remains the foundation of treatment for the majority of patients affected by advanced non­small cell lung cancer (NSCLC). However, DDP­resistance limits the clinical utility of this drug in patients with advanced NSCLC. The aim of the present study was to investigate the inhibitory effect of niclosamide on human lung cancer cell growth and to investigate the possible underlying mechanism. The effects of niclosamide on the proliferation of human lung adenocarcinoma (A549) and DDP­resistant (CR) human lung adenocarcinoma (A549/DDP) cells were examined by Cell Counting kit­8 assay. The impact of niclosamide on the apoptosis of A549/DDP cells was detected by Annexin V­fluorescein isothiocyanate/propidium iodide assay. The expression levels of cisplatin­resistant­associated molecules (lung resistance­related protein and c­myc) following niclosamide treatment in A549/DDP cells were evaluated by western blot analysis. The results indicated that niclosamide in combination with DDP demonstrated a synergistic effect in A549/DDP cells and directly induced apoptosis, which may be associated with caspase­3 activation. Furthermore, niclosamide decreased the expression level of c­myc protein, which may influence DDP sensitivity of A549/DDP cells. Thus, the present study indicates that niclosamide combined with DDP exerts a synergistic effect in cisplatin­resistant lung cancer cells and may present as a promising drug candidate in lung cancer therapy.

Enhanced expression of SETDB1 possesses prognostic value and promotes cell proliferation, migration and invasion in nasopharyngeal carcinoma.

SETDB1, an H3K9­specific histone methyltransferase, has been described as a repressed transcription marker which triggers tumorigenesis of many types of human cancer. However, there are few studies elucidating the relationship between SETDB1 and nasopharyngeal carcinoma. In the present study, we confirmed that SETDB1 exhibited higher expression levels in nasopharyngeal carcinoma (NPC) tissues and cell lines, compared to these levels in non­tumor tissues and a normal human nasopharyngeal epithelial cell line. Kaplan­Meier analysis showed that higher SETDB1 expression indicated an unfavorable prognosis for NPC patients, making it an independent prognostic factor for NPC in the COX proportional hazards model. In vitro functional studies revealed that upregulation of SETDB1 expression in CNE1 cells promoted cell proliferation, possibly through cell cycle G1/S phase transition. Moreover, it also enhanced cell migration and invasion ability. Downregulation of SETDB1 expression in 5­8F cells resulted in the opposite response. Overall, the findings indicated that increased expression of SETDB1 may predict poor overall survival and the malignant phenotype of NPC.

Niclosamide enhances the antitumor effects of radiation by inhibiting the hypoxia-inducible factor-1α/vascular endothelial growth factor signaling pathway in human lung cancer cells.

Lung cancer is one of the leading causes of cancer-associated mortality, worldwide. The overall survival rate remains low, but progress has been made in improving the diagnosis and treatment of lung cancer over the past decades. Niclosamide, a salicylanilide derivative used for the treatment of tapeworm infections, is safe, well tolerated, inexpensive and readily available. Previous studies have identified niclosamide as a potential anticancer agent. The present study demonstrated that niclosamide enhanced the effect of irradiation by inhibiting the hypoxia-inducible factor-1α/vascular endothelial growth factor signaling pathway. These findings suggest that niclosamide may be a promising candidate for clinical evaluation as part of a combined regimen for the treatment of non-small cell lung cancer.

Combination of gambogic acid with cisplatin enhances the antitumor effects on cisplatin-resistant lung cancer cells by downregulating MRP2 and LRP expression.

Cisplatin resistance is a main clinical problem of lung cancer therapy. Gambogic acid (GA) could prohibit the proliferation of a variety of human cancer cells. However, the effects of GA on cisplatin-resistant lung cancer are still unclear. The objective of the present study was to find out the antitumor effects of GA on cisplatin-resistant human lung cancer A549/DDP cells and further explore its underlying mechanisms. Cell Counting Kit-8 assay was used to observe the impacts of GA and/or cisplatin on the proliferation of lung cancer cells; flow cytometry was used to detect the effects of GA on cell cycle and apoptosis; Western blot was used to examine the effects of GA on the expression of lung resistance protein (LRP) and multidrug resistance-associated protein 2 (MRP2) protein in A549/DDP cells. Our results showed that GA dose- and time-dependently prohibited the proliferation and induced significant cell apoptosis in A549 and A549/DDP cells. GA also induced G0/G1 arrest in both A549/DDP and A549 cells. Moreover, GA upregulated protein expression level of cleaved caspase-3 and Bax and downregulated protein expression level of pro-caspase-9 and Bcl-2 in time- and dose-dependent way in A549/DDP cells. GA combined with cisplatin enhanced the cells apoptotic rate and reduced the cisplatin resistance index in A549/DDP cells. In addition, GA reduced the MRP2 and LRP protein expression level in A549/DDP cells. GA inhibits the proliferation, induces cell cycle arrest and apoptosis in A549/DDP cells. Combination of GA with cisplatin enhances the antitumor effects on cisplatin-resistant lung cancer cells by downregulating MRP2 and LRP expression.