National Centre for Cell Science, Pune, India.
Integr Cancer Ther. 2011 Dec;10(4):NP4-14. doi: 10.1177/1534735411423922. Epub 2011 Oct 11.
Hepatocellular carcinoma (HCC) is a common malignancy worldwide and has an annual occurrence of one million new cases. Novel therapeutic strategies of increased efficacy in the treatment of HCC-bearing patients would certainly be helpful. Hence, the authors explored the effect of combination treatment of roscovitine with chemotherapeutic drugs or quercetin (Qctn) in hepatoma cells, HepG2 and Hep3B.
Cell viability was assessed by MTT assay, cell growth assay, and nuclear morphological changes by DAPI staining. The altered expression of signaling proteins and apoptotic molecules was established by Western blotting.
Roscovitine pretreatment considerably enhanced the drugs and Qctn-induced cell death in HepG2 and Hep3B cells. The exploratory studies revealed that augmented cell killing in HepG2 and Hep3B was mediated via Akt pathway and was independent of p53. pAkt was found to be significantly downregulated in combination treatment of roscovitine with carboplatin or Qctn. Corresponding to reduced expression of pAkt, the downstream molecules Bcl-2 and proactive forms of caspase 9 and caspase 3 were also downregulated indicating apoptosis.
The present study reports for the first time, in hepatoma cells, the potentiation of carboplatin- and Qctn-induced cell death by the cell cycle inhibitor roscovitine. Roscovitine can thus be considered as a potential therapeutic target in combination with chemotherapeutic drugs or Qctn for treatment of HCC.
肝细胞癌（HCC）是一种常见的恶性肿瘤，全球每年有 100 万例新发病例。新型治疗策略如果能提高 HCC 患者的治疗效果，肯定会有所帮助。因此，作者探索了联合使用罗司维亭与化疗药物或槲皮素（Qctn）治疗肝癌细胞 HepG2 和 Hep3B 的效果。
通过 MTT 测定法、细胞生长测定法和 DAPI 染色检测细胞核形态变化来评估细胞活力。通过 Western blot 检测信号蛋白和凋亡分子的表达变化。
罗司维亭预处理可显著增强化疗药物和顺铂或 Qctn 在 HepG2 和 Hep3B 细胞中的细胞毒性。探索性研究表明，在 HepG2 和 Hep3B 中增强的细胞杀伤作用是通过 Akt 途径介导的，与 p53 无关。联合使用罗司维亭与顺铂或 Qctn 可显著下调 pAkt。相应地，pAkt 的下调导致下游分子 Bcl-2 和 caspase 9 和 caspase 3 的前体形式也下调，表明发生了细胞凋亡。
本研究首次在肝癌细胞中报告了细胞周期抑制剂罗司维亭增强顺铂和 Qctn 诱导的细胞死亡的作用。因此，罗司维亭可以与化疗药物或 Qctn 联合作为治疗 HCC 的潜在治疗靶点。
