摘要
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、DNA ladder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;western-blot法检测CIP-36对KBV200细胞P-gp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,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。Western-blot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。
Objective： To study the antitumor activity of CIP-36 on multidrug resistance human oral squamous carcinoma cells （KBV 200 cells） in vitro and the feasible anticancer mechanisms. Methods： MTT assay, morphological study, DNA gel electrophoresis, flow cytometry, western-blot, and immunofluorescence were carded out. Results： The IC50 value of CIP-36 on KBV 200 cells was （2.06 ± 0.38） μmol / L. After treated with CIP-36, the apparent morphological characteristic and typical DNA ladder of KBV 200 cells 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 KBV 200 cell line.
出处
《药物评价研究》
CAS
2010年第4期267-271,共5页
Drug Evaluation Research
基金
国家自然科学基金(No30873363)
天津市自然科学基金重点资助项目(No08JCYBJC070000)
天津市自然科学重点支持项目(No09ZCKFNC01200)
