目的：研究鬼臼毒素衍生物CIP-36對多藥耐藥人口腔鱗狀上皮癌細胞KBV 200的抗腫瘤活性及其作用機制。方法：MTT法考察CIP-36對KBV 200體外增殖的抑制作用；Giemsa染色、DNA ladder和流式細胞儀等方法進行細胞凋亡檢測；免疫熒光法觀察CIP-36對細胞骨架的作用；western-blot法檢測CIP-36對KBV 200細胞P-gp表達的影響。結果：CIP-36對KBV 200細胞有明顯的抑制作用，IC₅₀值為（2.06±0.38）μmol / L，能夠誘導細胞產(chǎn)生凋亡小體和DNA ladder。流式細胞檢測到了細胞凋亡峰，并觀察到細胞周期出現(xiàn)S/G₂+M期阻滯。Western-blot結果顯示P-gp表達降低，并且觀察到CIP-36可破壞KBV 200細胞的細胞骨架。結論：CIP-36可能通過降低P-gp的表達，破壞細胞骨架等多靶點克服KBV 200細胞株的多藥耐藥性。

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 carried 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.

國家自然科學基金（No 30873363）；天津市自然科學基金重點資助項目（No 08JCYBJC070000）；天津市自然科學重點支持項目（No 09ZCKFNC01200）