National Key Disciplines of Otorhinolaryngology, Otorhinolaryngology Hospital, Otorhinolaryngology Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangdong, P.R. China.
Oncol Res. 2009;18(2-3):73-81. doi: 10.3727/096504009789954618.
The cytotoxic effects and mechanism of action of cisplatin and the mTOR inhibitor rapamycin on Hep-2 laryngeal cancer cells were investigated. Hep-2 cells were cultured in the presence of different concentrations of rapamycin, cisplatin, or the two combined. Inhibition of cell growth, apoptosis, and AKT, mTOR, S6K, and ERCC1 protein levels were assessed. All combinations of rapamycin and cisplatin resulted in synergistic inhibition of cell growth (as indicated by q values determined using Jin's formula > 1.15). Rapamycin inhibited Hep-2 cell growth, induced G1 arrest, and when combined with cisplatin, enhanced apoptosis. p-mTOR and S6K expressions were significantly downregulated by rapamycin. ERCC1 expression was significantly upregulated with cisplatin treatment. Combined cisplatin and rapamycin treatment resulted in significant downregulated p-mTOR and S6K expression, but no change in ERCC1 expression. Rapamycin and cisplatin act in a synergistic manner, increasing the cytotoxic effect on Hep-2 cells. Rapamycin may facilitate increased Hep-2 cell apoptosis with cisplatin via inhibiting downstream expression of proteins in the AKT-mTOR signaling pathway.
研究了顺铂和 mTOR 抑制剂雷帕霉素对 Hep-2 喉癌细胞的细胞毒性作用和作用机制。在不同浓度的雷帕霉素、顺铂或两者联合存在的情况下培养 Hep-2 细胞。评估细胞生长抑制、细胞凋亡以及 AKT、mTOR、S6K 和 ERCC1 蛋白水平。雷帕霉素和顺铂的所有组合均导致细胞生长的协同抑制（如 Jin 公式确定的 q 值> 1.15 所示）。雷帕霉素抑制 Hep-2 细胞生长，诱导 G1 期阻滞，与顺铂联合使用时增强细胞凋亡。雷帕霉素显著下调 p-mTOR 和 S6K 的表达。顺铂处理可显著上调 ERCC1 的表达。顺铂和雷帕霉素联合治疗导致 p-mTOR 和 S6K 的表达显著下调，但 ERCC1 的表达没有变化。雷帕霉素和顺铂以协同方式发挥作用，增加对 Hep-2 细胞的细胞毒性作用。雷帕霉素可能通过抑制 AKT-mTOR 信号通路下游蛋白的表达来促进顺铂诱导的 Hep-2 细胞凋亡。
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