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目的:通过检测组蛋白去乙酰化酶抑制剂(SAHA)联合顺铂(DDP)对宫颈癌SiHa细胞生长抑制和促凋亡结果,探讨SAHA对宫颈癌细胞化疗增敏的疗效及机制。方法:将SAHA 0.25、0.5、1、2、4、6μmol/L和DDP 1、2、4、6、8、10μg/mL分别组成单药组和不同SAHA+DDP联合用药组,另设不加药对照组。MTT法检测两种药物单用及联合用药对SiHa细胞的增殖抑制作用;通过流式细胞术(FCM)观察药物对细胞周期的影响;用AnnexinV-FITC标记药物作用后的细胞,了解其早期凋亡情况;镜检观察药物作用后细胞形态的变化。结果:SAHA有抑制癌细胞生长的作用,两药联合具有协同作用或相加作用(P<0.05);SAHA使细胞停滞在G1/G0期,与DDP联合作用后凋亡率增加,使细胞周期进一步阻滞在G1/G0期(P<0.05)。镜下可见对照组癌细胞生长旺盛,异型性高,SA-HA组与DDP组则可见细胞缩小变形,胞膜皱缩,贴壁不良,肿瘤细胞大量坏死,联用组尤为明显。结论:SAHA联合DDP可以抑制细胞增殖,停滞细胞周期,促进细胞凋亡,二者联合有协同作用。
Objective: To investigate the effect and mechanism of SAHA on chemosensitivity of cervical cancer cells by detecting the effect of histamine deacetylase inhibitor (SAHA) and cisplatin (DDP) on the growth inhibition and apoptosis of cervical cancer SiHa cells. Methods: SAHA 0.25, 0.5, 1, 2, 4, 6μmol / L and DDP 1,2,4,6,8,10μg / mL were divided into single drug group and different SAHA + DDP combined drug group, Drug control group. MTT assay was used to detect the proliferation inhibition of SiHa cells by single or combination of two drugs. The effects of drugs on cell cycle were observed by flow cytometry (FCM). The cells were labeled with Annexin V-FITC Death situation; microscopic examination of the changes in cell morphology after the drug effect. Results: SAHA could inhibit the growth of cancer cells. The combination of the two drugs had a synergistic effect or additive effect (P <0.05). SAHA arrested cells in G1 / G0 phase and increased the apoptosis rate after combined with DDP, Further arrest in G1 / G0 phase (P <0.05). Microscopically, the control group showed strong growth of cancer cells and high atypia. SA-HA group and DDP group showed shrinkage of cells, shrinkage of cell membrane, poor adherence, and massive necrosis of tumor cells, especially in combination group. Conclusion: SAHA combined with DDP can inhibit cell proliferation, arrest cell cycle and promote apoptosis, and the combination of both can have synergistic effect.