Dynamic influence of Rhein lysinate on HeLa cells.

In a previous study, it was demonstrated that Rhein lysinate (RHL) inhibited HeLa cell proliferation via a specific mechanism. The aim of the present study was to clarify the mechanism of RHL by investigating its effect on mitochondrial damage and cell apoptosis. The results indicated that RHL inhibited cell growth and proliferation in HeLa cells. HeLa cells treated with RHL developed extensive vacuolization in a dose- and time-dependent manner. Ultrastructure analysis using transmission electron microscopy revealed that the vacuoles observed were damaged mitochondria and endoplasmic reticulum. The effects of RHL on mitochondria were further confirmed by a decrease in mitochondrial membrane potential and increased generation of reactive oxygen species. The mitochondrial proteome was analyzed, and the results demonstrated that the expression of the cytoskeletal protein keratin and dermal papilla derived protein 12 (associated with the oxidation-reduction process), which are associated with mitochondrial structure and function, were decreased compared with the untreated control group. Hoechst staining, flow cytometry and western blotting also revealed that apoptosis was induced at 24 h following RHL treatment. These results confirm that RHL toxicity in HeLa cells is a dynamic process. Vacuolar degeneration appeared in HeLa cells treated with 160 µmol/l RHL during the first 6 h and with the extension of RHL treatment, cell apoptosis was presented at ~24 h in HeLa cells.

Associations of nicotinamide N-methyltransferase gene single nucleotide polymorphisms with sport performance and relative maximal oxygen uptake.

To observe the associations between single nucleotide polymorphisms (SNPs) of nicotinamide N-methyltransferase (NNMT) gene and sport performance and to analyse genotype associations of the associated SNPs with sport performance and relative maximal oxygen uptake ([Formula: see text]). Participants were selected from 685 Chinese Han male college students. The completion times of a 1000-m run and a 50-m run were used to reflect sport performance, respectively. Nineteen tagSNPs were genotyped with Polymerase chain reaction-ligase detection reaction. Relative [Formula: see text] was directly determined with a cardiopulmonary function analyser. A significant association was found between rs2256292 and 1000-m run performance, but no significant association was found between any tagSNPs and 50-m run performance. The genotype associations of rs2256292 with 1000-m run performance and with relative [Formula: see text] were both significant under the recessive model (CC vs. CG + GG). No tagSNP in NNMT is significantly associated with 50-m run performance but rs2256292 is significantly associated with 1000-m run performance. The genotype associations of rs2256292 with sport performance are significant under recessive model, and a higher relative [Formula: see text] may be the physiological reason for minor homozygote CC carriers being of the better 1000-m runners.

Physiological Study on Association between Nicotinamide N-Methyltransferase Gene Polymorphisms and Hyperlipidemia.

Nicotinamide N-methyltransferase (NNMT) catalyzes the methylation of nicotinamide. Our previous works indicate that NNMT is involved in the body mass index and energy metabolism, and recently the association between a SNP (rs694539) of NNMT and a variety of cardiovascular diseases was reported. At present, more than 200 NNMT single nucleotide polymorphisms (SNPs) have been identified in the databases of the human genome projects; however, the association between rs694539 variation and hyperlipidemia has not been reported yet, and whether there are any SNPs in NNMT significantly associated with hyperlipidemia is still unclear. In this paper, we selected 19 SNPs in NNMT as the tagSNPs using Haploview software (Haploview 4.2) first and then performed a case-control study to observe the association between these tagSNPs and hyperlipidemia and finally applied physiological approaches to explore the possible mechanisms through which the NNMT polymorphism induces hyperlipidemia. The results show that a SNP (rs1941404) in NNMT is significantly associated with hyperlipidemia, and the influence of rs1941404 variation on the resting energy expenditure may be the possible mechanism for rs1941404 variation to induce hyperlipidemia.

Antitumor activity of rhein lysinate against human glioma U87 cells in vitro and in vivo.

In previous studies, we demonstrated that rhein lysinate (RHL), the salt of rhein and lysine that is easily dissolved in water, inhibited the growth of tumor cells derived from breast and ovarian cancer, hepatocellular carcinoma, cervical cancer and lung carcinoma. Based on these observations, human glioma U87 cells and a xenograft model in BALB/c nude mice were used to examine the antitumor activity of RHL against human glioma. Notably, RHL statistically significantly suppressed the growth of human glioma U87 xenografts in BALB/c nude mice. In vitro, there was a significant reduction in cell proliferation after treatment with RHL in a dose- and time-dependent manner. The overall growth inhibition was correlated with the increase in reactive oxygen species (ROS) production and cell apoptosis. The apoptosis- and cell cycle-related proteins including BAX and Bim were increased, whereas Bcl-2 and cyclin D were decreased in the RHL-treated cells. The results demonstrated that RHL is highly effective against the growth of human glioma U87 xenografts in BALB/c nude mice. The potent antitumor activity of RHL may be mediated through downregulation of Bcl-2 and cyclin D expression and upregulation of BAX and Bim expression.

Gambogic Acid lysinate induces apoptosis in breast cancer mcf-7 cells by increasing reactive oxygen species.

Gambogic acid (GA) inhibits the proliferation of various human cancer cells. However, because of its water insolubility, the antitumor efficacy of GA is limited. Objectives. To investigate the antitumor activity of gambogic acid lysinate (GAL) and its mechanism. Methods. Inhibition of cell proliferation was determined by MTT assay; intracellular ROS level was detected by staining cells with DCFH-DA; cell apoptosis was determined by flow cytometer and the mechanism of GAL was investigated by Western blot. Results. GAL inhibited the proliferation of MCF-7 cells with IC50 values 1.46 µmol/L comparable with GA (IC50, 1.16 µmol/L). GAL promoted the production of ROS; however NAC could remove ROS and block the effect of GAL. GAL inhibited the expression of SIRT1 but increased the phosphorylation of FOXO3a and the expression of p27Kip1. At knockdown of FOXO3a, cell apoptosis induced by GAL can be partly blocked. In addition it also enhanced the cleavage of caspase-3. Conclusions. GAL inhibited MCF-7 cell proliferation and induced MCF-7 cell apoptosis by increasing ROS level which could induce cell apoptosis by both SIRT1/FOXO3a/p27Kip1 and caspase-3 signal pathway. These results suggested that GAL might be useful as a modulation agent in cancer chemotherapy.

KNDC1 knockdown protects human umbilical vein endothelial cells from senescence.

KNDC1 (kinase noncatalytic C-lobe domain containing 1), a brain-specific Ras guanine nucleotide exchange factor, controls the negative regulation of neuronal dendrite growth. However, the effect of KNDC1 on cellular senescence remains to be elucidated. The present study investigated the impact of KNDC1 knockdown on human endothelial cell senescence and the mechanisms underlying this effect. Human umbilical vein endothelial cells (HUVECs) cultured in vitro were used as a model of biological aging. Senescence­associated ß-galactosidase staining was used to detect cellular senescence and flow cytometry was employed to determine cell cycle progression. Quantitative polymerase chain reaction (qPCR) and western blot analysis were utilized to investigate mRNA transcription and protein expression. In the HUVECs, a senescence-like phenotypes developed with increasing passage number in vitro, which were associated with a progressive increase in the transcription and expression of KNDC1. KNDC1 knockdown promoted cell proliferation and partially reversed cellular senescence and cell cycle arrest in the G0/G1 phase in aging HUVECs. Investigations into the mechanism underlying this effect demonstrated that KNDC1 knockdown promoted HUVEC proliferation via the extracellular signal-regulated kinase signaling pathway and delayed HUVEC senescence by inhibiting the p53-p21-p16 transduction cascade. In addition, the promotion of the capillary tube network formation and the increased expression of endothelial nitric oxide synthase revealed that the activity and function of endothelial cells were enhanced. In conclusion, KNDC1 knockdown delayed endothelial cell senescence and promoted HUVEC activity and function. These results demonstrated that KNDC1 may be a novel therapeutic target for the development of agents to extend human life.

Synergy of Taxol and rhein lysinate associated with the downregulation of ERK activation in lung carcinoma cells.

In previous studies we observed that rhein lysinate (RHL), a salt of rhein and lysine that is easily dissolved in water, inhibited the growth of tumor cells in breast cancer, ovarian cancer, hepatocellular carcinoma and cervical cancer. The present study aimed to investigate the effects of RHL on H460 and A549 non-small cell lung cancer (NSCLC) cells using a combination of RHL and Taxol. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was used to determine the growth inhibition effect of the drugs in the H460 and A549 cells. Cell apoptosis was analyzed by flow cytometry combined with fluorescein-isothiocyanate-Annexin V/propidium iodide (PI) staining. The expression levels of proteins were detected by western blotting. There was a significant reduction in the proliferation of the NSCLC cell lines treated with a combination of Taxol and RHL. The overall growth inhibition was directly correlated with apoptotic cell death. RHL potentiated Taxol-induced cell killing by reducing extracellular signal-regulated kinase (ERK) activity and increasing the levels of cleaved poly(ADP-ribose) polymerase (PARP) and caspase-3. Notably, the results for the Bcl-2 and NF-κB proteins also showed downregulation in the combined treatment group compared with the single-agent treatment and the untreated control groups. The present results showed that RHL potentiates the growth inhibition induced by Taxol in NSCLC cells and showed that this synergy may be associated with the downregulation of ERK activation.

Rhein lysinate decreases the generation of ß-amyloid in the brain tissues of Alzheimer's disease model mice by inhibiting inflammatory response and oxidative stress.

The protective effect of rhein lysinate (RHL) on Alzheimer's disease (AD) was explored in senescence-accelerated mouse prone-8 (SAMP8) mice. SAMP8 mice without treatment were used as the AD-positive control, and senescence-accelerated-resistant mice were used as the AD-negative control. In this study, 4-month-old male SAMP8 mice were orally administered 25 and 50 mg/kg RHL in drinking water for 6 months. The results of brain tissue enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and Western blot were demonstrated that compared with SAMP8 group, ß-amyloid1-40 and ß-amyloid1-42 were reduced; the levels of tumor necrosis factor-α and interleukin 6 of brain tissues were also significantly decreased; however, the level of sirtuin 1 (SIRT1) was increased in the RHL-treated group. Compared with SAMP8 group, the ROS levels and malondialdehyde levels were decreased; however, superoxide dismutase and glutathione peroxidase levels were increased in the brain tissues of SAMP8 25 and 50 mg/kg RHL-treated groups. In conclusion, the reduction of Aß induced by RHL was related to the increase of SIRT1 and the inhibition of the inflammatory response and oxidative stress in SAMP8 mice. It might be a promising biological therapeutic drug for AD.

Astragalus polysaccharides suppress ICAM-1 and VCAM-1 expression in TNF-α-treated human vascular endothelial cells by blocking NF-κB activation.

AIM: To investigate the effects Astragalus polysaccharides (APS) on tumor necrosis factor (TNF)-α-induced inflammatory reactions in human umbilical vein endothelial cells (HUVECs) and to elucidate the underlying mechanisms. METHODS: HUVECs were treated with TNF-α for 24 h. The amounts of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were determined with Western blotting. HUVEC viability and apoptosis were detected using cell viability assay and Hoechst staining, respectively. Reactive oxygen species (ROS) production was measured by DHE staining. Monocyte and HUVEC adhesion assay was used to detect endothelial cell adhesive function. NF-κB activation was detected with immunofluorescence. RESULTS: TNF-α (1-80 ng/mL) caused dose- and time-dependent increases of ICAM-1 and VCAM-1 expression in HUVECs, accompanied by significant augmentation of IκB phosphorylation and NF-κB translocation into the nuclei. Pretreatment with APS (10 and 50 µg/mL) significantly attenuated TNFα-induced upregulation of ICAM-1 VCAM-1 and NF-κB translocation. Moreover, APS significantly reduced apoptosis, ROS generation and adhesion function damage in TNF-α-treated HUVECs. CONCLUSION: APS suppresses TNFα-induced adhesion molecule expression by blocking NF-κB signaling and inhibiting ROS generation in HUVECs. The results suggest that APS may be used to treat and prevent endothelial cell injury-related diseases.

Bortezomid enhances the efficacy of lidamycin against human multiple myeloma cells.

The proteasome inhibitor bortezomib has been applied successfully to treat multiple myeloma (MM). Its synergistic effects with other anticancer drugs have been studied widely. In the present study, it was found that lidamycin (LDM), a member of the enediyne antibiotic family, showed much more potent cytotoxicity than bortezomib to MM cell lines: U266 and SKO-007. Here, we investigated the potential synergy of bortezomib and LDM on MM cells. The results showed that cotreatment of bortezomib and LDM synergistically induced cytotoxicity and apoptosis in MM cell lines, followed by enhanced caspase-3 cleavage and degradation of poly-ADP-ribose polymerase together with the decreased nuclear factor-κB protein. These two drugs synergistically induced apoptosis, which was associated with enhanced activation of two mitogen-activated protein kinases: p38 mitogen-activated protein kinase and c-Jun NH(2)-terminal kinase. Moreover, bortezomib plus LDM synergistically induced apoptosis was also associated with downregulation of extracellular signal-regulated kinase, and induction of endoplasmic reticulum stress response. Overall, our results indicate that the combined regimen of bortezomib and LDM might be a potential therapeutic remedy for the treatment of MM.

Rhein lysinate increases the median survival time of SAMP10 mice: protective role in the kidney.

AIM: To investigate the protective effects of rhein lysinate (RHL), a major bioactive constituent of the rhizome of rhubarb (Rheum palmatum Linn or Rheum tanguticum Maxim), against kidney impairment in senescence-prone inbred strain 10 (SAMP10) mice. METHODS: SAMP10 mice were orally administered RHL (25 or 50 mg/kg) daily until 50% of the mice died. Senescence-resistant inbred strain 1 (SAMR1) mice administered no drug were taken as control. The kidneys were harvested after animal death, and examined morphologically and with immunochemical assays. The levels of MAD, SOD and GSH-px in the kidneys were measured with a photometric method. The expression of inflammatory factors and related proteins in the kidneys was analyzed using Western blotting. RESULTS: Treatment of SAMP10 mice with RHL had no effect on the body weight or phenotype. However, RHL significantly prolonged the median survival time of SAMP10 mice by approximately 25%, as compared to untreated SAMP10 mice. Compared SAMR1 mice, SAMP10 mice had a significantly lower level of SOD in the kidneys, but had no significant difference in the MDA or GSH-px levels. Treatment of SAMP10 mice with RHL significantly reduced the MAD level, and increased the SOD and GSH-px levels in the kidneys. Glomerulonephritis was observed in SAMP10 mice but not in SAMR1 mice. RHL decreased the incidence of glomerulonephritis, and significantly decreased the levels of TNF-α, IL-6, NF-κB, collagen types I and III in the kidneys. CONCLUSION: Accelerated senescence is associated with glomerulonephritis in SAMP10 mice, and RHL prolongs their median survival time by reducing the severity of glomerulonephritis.

Rhein lysinate induced S-phase arrest and increased the anti-tumor activity of 5-FU in HeLa cells.

Rhein lysinate (RHL), easily dissolved in water, is one of the anthraquinones, and has been shown to have anti-tumor activity in different human cancer cell lines. In the present study, we observed that RHL could cause vacuolar degeneration in HeLa cells, which was not observed in human umbilical vein endothelial cells (HUVECs) and other cell lines (SKOV-3 and SK-BR-3). Therefore, the purpose of this study was to investigate the anti-tumor effect of rhein lysinate on human cervix cancer HeLa cells. The results indicated that RHL could induce HeLa cell S-phase arrest and RHL (higher than 80 µM) also induced HeLa cell G2/M-phase arrest in a dose-dependent manner. Compared to the HeLa cells, RHL induced HUVECs G1-phase arrest at all dose levels tested in a dose-dependent manner. Treatment with RHL led to a significant S or G2/M-phase arrest through promoting the expression of p53 and p21 and the phosphorylation of p53. Moreover, 80 µM RHL could increase 5-FU anti-tumor activity. In conclusion, RHL could be a novel chemotherapeutic drug candidate for the treatment of human cervix cancer in the future.

Rhein lysinate inhibits cell growth by modulating various mitogen-activated protein kinases in cervical cancer cells.

In previous studies, we found that rhein lysinate (RHL; the salt of rhein and lysine, easily dissolved in water) inhibited the growth of tumor cells in breast and ovarian cancer and hepatocellular carcinoma. This study aimed to investigate the effect of RHL on the growth of human cervical carcinoma HeLa cells and any underlying mechanisms. RHL inhibited the growth of HeLa cells in a dose- and time-dependent manner. It was also noted that RHL induced apoptosis in HeLa cells in a dose-dependent manner. Mechanistically, RHL triggered HeLa cell apoptosis by increasing the levels of cleaved poly ADP-ribose polymerase (PARP) and caspase-3/7. In addition, the activation of p38 mitogen-activated protein kinase (MAPK) and c-Jun NH2-terminal kinase (JNK) was a critical mediator in RHL-induced growth inhibition. Inhibition of the expression of p38 MAPK and JNK by pharmacological inhibitors reversed RHL-induced growth inhibition by decreasing the level of cleaved PARP and caspase-3/7. Phosphorylation of the extracellular signal-related kinase (ERK) was increased by RHL; conversely, the MEK inhibitor which inhibits ERK activity, synergistically enhanced RHL-induced growth inhibition in HeLa cells. The results showed that RHL inhibits Hela cell growth through the activation of p38 MAPK and JNK, and is a potential chemotherapeutic agent for cervical cancer.

Rhein lysinate suppresses the growth of tumor cells and increases the anti-tumor activity of Taxol in mice.

In previous studies, rhein, one of the major bioactive constituents in the rhizome of rhubarb, inhibited the proliferation of various human cancer cells. However, because of its water insolubility, the anti-tumor efficacy of rhein was limited in vivo. In this study, we observed the anti-tumor activity of rhein lysinate (the salt of rhein and lysine easily dissolves in water) in vivo and investigated its mechanism. Inhibition of ovarian cancer SKOV-3 cell proliferation was determined by MTT assay and the mechanism of action of rhein lysinate was investigated by Western blot analysis. The therapeutic efficacy of rhein lysinate was evaluated by intragastric and intraperitoneal administrations in H22 hepatocellular carcinoma mice. Rhein lysinate inhibited the proliferation of SKOV-3 cells and the IC50 value was 80 microM. Rhein lysinate inhibited the phosphorylation of MEK and ERK and increased the anti-tumor activity of Taxol in vitro. It inhibited tumor growth by both intragastric and intraperitoneal administrations and improved the therapeutic effect of Taxol in H22 hepatocellular carcinoma mice. In conclusion, rhein lysinate offers an anti-tumor activity in vivo and is hopeful to be a chemotherapeutic drug.

Lidamycin shows highly potent cytotoxic to myeloma cells and inhibits tumor growth in mice.

AIM: To investigate the effects of lidamycin (LDM) on a mouse myeloma cell line (SP2/0) and human multiple myeloma cell lines (U266 and SKO-007), and provide the basis for the use of LDM in cancer therapy. METHODS: A 3-[4,5-dimethylthiazol-2-yl]5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]2H-tetrazolium inner salt (MTS) assay was used to determine the degree of growth inhibition by the drugs analyzed in this study. Cell cycle distribution and analysis were measured by flow cytometry combined with propidium iodide (PI) staining. The effects on apoptosis were measured by Hoechst 33342 staining and by flow cytometry combined with fluorescein-isothiocyanate-Annexin V/propidium iodide (FITC-Annexin V/PI) staining. Protein expression was determined by Western blot analysis. In vivo antitumor activity was measured using a murine myeloma model in BALB/c mice. RESULTS: There was a significant reduction in cell proliferation after treatment with LDM. The overall growth inhibition correlated with increased apoptotic cell death. LDM-induced cell apoptosis was associated with the activation of c-Jun-N-terminal kinase (JNK), and cleavage of caspase-3/7 and poly (ADP-ribose) polymerase (PARP). LDM markedly suppressed tumor growth in a murine myeloma model. CONCLUSION: LDM induces apoptosis in murine myeloma SP2/0 cells as well as in human myeloma U266 and SKO-007 cell lines. The sustained activation of JNK might play a critical role in LDM-induced apoptosis in the SP2/0 cell line. LDM demonstrates significant antitumor efficacy against myeloma SP2/0 cells in mice. Taken together, our data provide some clues for further research of the effects of LDM on human multiple myeloma.Acta Pharmacologica Sinica (2009) 30: 1025-1032; doi: 10.1038/aps.2009.75.

Enediyne lidamycin induces apoptosis in human multiple myeloma cells through activation of p38 mitogen-activated protein kinase and c-Jun NH2-terminal kinase.

In the present study, the effects of lidamycin (LDM), a member of the enediyne antibiotic family, on two human multiple myeloma (MM) cell lines, U266 and SKO-007, were evaluated. In MTS assay, LDM showed much more potent cytotoxicity than conventional anti-MM agents to both cell lines. The IC(50) values of LDM for the U266 and SKO-007 cells were 0.0575 +/- 0.0015 and 0.1585 +/- 0.0166 nM, respectively, much lower than those of adriamycin, dexamethasone, and vincristine. Mechanistically, LDM triggered MM cells apoptosis by increasing the levels of cleaved poly ADP-ribose polymerase (PARP) and caspase-3/7. In addition, activation of p38 mitogen-activated protein kinase (MAPK) and c-Jun NH2-terminal kinase (JNK) was a critical mediator in LDM-induced cell death. Inhibition of the expression of p38 MAPK and JNK by pharmacological inhibitors reversed the LDM-induced apoptosis through decreasing the level of cleaved PARP and caspase-3/7. Interestingly, phosphorylation of extracellular signal-related kinase was increased by LDM; conversely, MEK inhibitor synergistically enhanced LDM-induced cytotoxicity and apoptosis in MM cells. The results demonstrated that LDM suppresses MM cell growth through the activation of p38 MAPK and JNK, with the potential to be developed as a chemotherapeutic agent for MM.

Rhein lysinate suppresses the growth of breast cancer cells and potentiates the inhibitory effect of Taxol in athymic mice.

Earlier studies have shown that rhein, one of the major bioactive constituents of the rhizome of rhubarb, inhibits the proliferation of various human cancer cells. However, because of its water insolubility, the antitumor efficacy of rhein is limited in vivo. In this study, we studied the antitumor activity of rhein lysinate (the salt of rhein and lysine and easily dissolving in water) and its mechanism. Inhibition of breast cancer cell proliferation was determined by MTT assay and the mechanism of action of rhein lysinate was investigated by western blot analysis. The therapeutic efficacy of rhein lysinate was evaluated by human cancer xenografts in athymic nude mice. Rhein lysinate inhibited the proliferation of breast cancer cells (MCF-7, SK-Br-3, and MDA-MB-231). The IC50 values were 95, 80, and 110 micromol/l, respectively. Rhein lysinate inhibited the phosphorylation of epidermal growth factor receptor, MEK, and ERK with or without EGF stimulation. It also inhibited tumor growth and enhanced the therapeutic effect of Taxol on MCF-7 xenografts in athymic mice. Rhein lysinate inhibited the phosphorylation of epidermal growth factor receptor and MAPK signal pathway. These results suggest that rhein lysinate might be useful as a modulation agent in cancer chemotherapy.

[Rhein lysinate induces apoptosis in breast cancer SK-Br-3 cells by inhibiting HER-2 signal pathway].

This study is to investigate the effect of rhein lysinate on inducing human breast cancer cell line SK-Br-3 apoptosis and the role of HER-2 signal pathway in the apoptosis. MTT assay was used to detect SK-Br-3 cell proliferation. Cell cycle and apoptosis were analyzed by flow cytometry. The protein expression and the protein phosphorylation of HER-2 signal pathway were detected by Western blotting. The level of HER-2 mRNA was detected by RT-PCR and the level of HER-2 expression was also detected by immunofluorescence cytochemical methods. The results showed that rhein lysinate remarkably inhibited breast cancer SK-Br-3 cell proliferation. The IC50 value for 48 h treatment was 85 micromol x L(-1). Apoptosis in SK-Br-3 cells was induced by rhein lysinate in a dose dependent manner. The protein expressions of HER-2, NF-KB, and the protein phosphorylation of HER-2 were downregulated, however the protein expression of p53 and p21 was upregulated after rhein lysinate treatment. The level of HER-2 mRNA decreased by using RT-PCR assay and the level of HER-2 expression was also decreased by using immunofluorescence cytochemical assay after rhein lysinate treatment. It can be concluded that rhein lysinate could inhibit SK-Br-3 cell proliferation and induce apoptosis. HER-2/NF-kappaB/p53/p21 signal pathway might be involved in this process. Rhein lysinate has a good prospect to be an adjuvant chemotherapeutic drug.