Department of Gynecologic Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, PR China.
Department of Bone and Soft-Tissue Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, PR China.
Biomed Pharmacother. 2017 May;89:1172-1177. doi: 10.1016/j.biopha.2017.03.012. Epub 2017 Mar 14.
The aim of the present study was utilizing Xiaoaiping as a single agent or combined with cisplatin to study its effect on the ovarian cancer cells (HO-8910 and HO-8910PM cells) in tumor cell proliferation, cell apoptosis, cell cycle distribution and cell invasion and migration.
Both HO-8910 and HO-8910PM cell lines were treated with Xiaoaiping injection, cisplatin or combination. Effects on the cell viability and apoptosis induction were estimated using the Cell counting Kit-8 assay and Annexin V-FITC/Propidium Iodide staining. The distribution of cells in different phases of the cell cycle was assayed using flow cytometry analysis. The effects of Xiaoaiping on the inhibition of cell invasion and migration were researched with Transwell cell migration.
Both Xiaoaiping and cisplatin significantly decreased the HO-8910 cell survival versus control arm. Combination treatment showed a higher cytotoxicity to cells in vitro than Xiaoaiping and cisplatin alone. An increase in the G0/G1 phase fraction in HO-8910 cells treated with either Xiaoaiping or cisplatin alone was evident when compared to the fraction in control arm. Compared to the effects of treatment with either agent alone, combination treatment significantly increased the fraction of cells in G0/G1 phase. The HO-8910 cell lines treated with cisplatin demonstrated a significant increase of apoptotic cell rate compared to untreated cell lines. The rate of apoptosis in combined treatment group was significantly higher than that of the single agent treatment groups. A significant reduction in the number of invading cells was observed for Xiaoaiping-treated HO-8910 cells compared with the control group. However, cisplatin did not significantly induce the migration of cells versus untreated cells. Combination of Xiaoaiping and cisplatin significantly suppressed cell invasion and migration versus single-drug treatment in HO-8910 cells. The results of HO-8910PM cells were similar with HO-8910 cells in all tests.
In summary, our results showed that Xiaoaiping as a single agent or combined with cisplatin could induce cell cycle arrest, cause apoptosis and necrosis in ovarian cancer cells, and inhibit cell invasion and migration. The present study also laid a foundation for further investigation involving molecular mechanism. Above all, it may provide a novel therapeutic regimen for ovarian cancer.
本研究旨在利用消癌平注射液（Xiaoaiping injection）作为单一药物或与顺铂（cisplatin）联合应用，研究其对卵巢癌细胞（HO-8910 和 HO-8910PM 细胞）的增殖、细胞凋亡、细胞周期分布、细胞侵袭和迁移的影响。
采用消癌平注射液、顺铂或联合处理 HO-8910 和 HO-8910PM 细胞系。用细胞计数试剂盒-8（Cell counting Kit-8 assay）和 Annexin V-FITC/碘化丙啶（Propidium Iodide staining）染色法评估细胞活力和诱导凋亡的效果。用流式细胞术分析细胞周期各时相的分布。用 Transwell 细胞迁移实验研究消癌平对细胞侵袭和迁移的抑制作用。
消癌平和顺铂均显著降低 HO-8910 细胞的存活率，与对照组相比。联合治疗对细胞的体外细胞毒性高于消癌平和顺铂单独作用。与对照组相比，单独用消癌平和顺铂处理的 HO-8910 细胞 G0/G1 期细胞分数明显增加。与单独用任一药物治疗相比，联合治疗显著增加了 G0/G1 期细胞的比例。与未处理的细胞系相比，用顺铂处理的 HO-8910 细胞系的凋亡细胞率显著增加。联合治疗组的细胞凋亡率明显高于单药治疗组。与对照组相比，用消癌平处理的 HO-8910 细胞的侵袭细胞数明显减少。然而，顺铂对未处理细胞的迁移没有明显的诱导作用。与单药治疗相比，联合应用消癌平和顺铂可显著抑制 HO-8910 细胞的侵袭和迁移。HO-8910PM 细胞的结果与 HO-8910 细胞在所有测试中相似。
综上所述，我们的研究结果表明，消癌平作为单一药物或与顺铂联合应用可诱导卵巢癌细胞周期阻滞，引起细胞凋亡和坏死，并抑制细胞侵袭和迁移。本研究还为进一步涉及分子机制的研究奠定了基础。最重要的是，它可能为卵巢癌提供一种新的治疗方案。
