鬼臼毒素衍生物CIP-36诱导KBV200细胞凋亡

CIP-36,a novel podophyllotoxin derivative,induces the apoptosis of KBV200 cells

目的研究鬼臼毒素衍生物CIP-36对多药耐药人口腔鳞状上皮癌细胞KBV200的抗肿瘤活性及其作用机制。方法MTT法考察CIP-36对KBV200体外增殖的抑制作用;Giemsa染色、DNAladder和流式细胞仪等方法进行细胞凋亡检测;免疫荧光法观察CIP-36对细胞骨架的作用;West-ernblot法检测CIP-36对KBV200细胞P-glycoprotein表达的影响。结果CIP-36对KBV200细胞有明显的抑制作用,IC50值为(2.06±0.38)μmol.L-1,能够诱导细胞产生凋亡小体和DNAladder。流式细胞检测到了细胞凋亡峰,并观察到细胞周期出现S/G2+M期阻滞。Westernblot结果显示P-gp表达降低,并且观察到CIP-36可破坏KBV200细胞的细胞骨架。结论CIP-36可能通过降低P-gp的表达,破坏细胞骨架等多靶点克服KBV200细胞株的多药耐药性。

Aim To study the antitumor activity of CIP-36 on multidrug resistance human oral squamous carcinoma cell（KBV200 cells）in vitro and the feasible anticancer mechanisms.Methods MTT assay,morphological study,DNA gel electrophoresis,flow cytometry,Western blot,and immunofluorescence were carried out.Results：The IC50 value of CIP-36 on KBV200 cells was（2.06±0.38）μmol·L^-1.After KBV200 cells were treated by CIP-36,the apparent morphological characteristic and typical DNA ladder were all detected.Both the number of apoptosis cells and the cell cycle were measured by flow cytometric.A typical ＂Sub-G1 peak＂ was checked and CIP-36 blocked the cell cycle at S/G2＋M phase.Western-blot showed that the expression of P-glycoprotein was decreased.CIP-36 could interfere with microtubule polymerization and disrupt cytoskeleton.Conclusions CIP-36 has the potentiality to overcome P-glycoprotein-mediated multidrug resistance in the KBV200 cell line.