Sensitizing effect of chemotherapy of isorhapontigenin through down-regulating expression of X-linked inhibitor of apoptosis / 中国药学杂志

ABSTRACT

OBJECTIVE: To observe the inhibitor effects of isorhapontigenin (ISO) on the proliferation of bladder cancer cells and expression of X-linked inhibitor of apoptosis (XIAP), and the sensitizing effect of chemotherapy of docetaxel to bladder cancer cells In ISO. METHODS: The ATPase assay and anchorage-independent growth assay were used to detect the cytotoxicity and proliferative capacity of ISO on the T24T bladder cancer cell line, respectively. The reverse transcription polymerase chain reaction (RT-PCR) and Western-blotting methods were used to detect XIAP gene expression after pretreated with ISO. Pretreatment with different concentration of docetaxel and ISO on T24T bladder cancer cell, ATPase methods were performed to measure in vitro cell viability. And the morphological changes and apoptosis rates were detected by phase contrast microscope and flow cytometry assay, respectively. RESULTS: ISO could exhibit significant inhibitory effects on human bladder cancer cell growth through ATPase assay and anchorage-independent growth assay. Further proved by Western-blotting and RT-PCR methods, the protein and mRNA level of XIAP gene in T24T cells were both significantly decreased. After pretreatment with ISO, the IC50 of T24T cells for docetaxel was (1.02 ± 0.38) nmol · L-1, significantly lower than that docetaxel without ISO, which was (8.78 ± 1.32) nmol · L-1 for 24 h( P < 0.01). Compared with the control group, the typical apoptosis morphological changes were observed in the T24T cells pretreatment with ISO combined with docetaxel. And the index of apoptosis was (21.07 ± 2.79)% at 2.5 nmol · L-1 docetaxel, markedly lower than those of T24T cells pretreatment with 2.5 nmol · L-1 docetaxel and ISO, which was (49.59 ± 5.67)% (P < 0.01). CONCLUSION: ISO could exhibit significant inhibitor) effects on human bladder cancer cell proliferation. And the XIAP gene could be down-regulated significantly by ISO, which could increase docetaxel-induced apoptosis and cytotoxic activity significantly.