Zhou Jin, Jiang Yuan-Yuan, Wang Hai-Ping, Chen Huan, Wu Yi-Chao, Wang Long, Pu Xiang, Yue Guizhou, Zhang Li
College of Science, Sichuan Agricultural University, Ya'an, China.
College of Life Science, China West Normal University, Nanchong, China.
Ann Transl Med. 2020 Jun;8(12):752. doi: 10.21037/atm-20-4072.
Paclitaxel is a widely used clinical first line chemotherapy drug for ovarian carcinoma. Tanshinone I (Tan-I) is one of the vital fat-soluble components, which derived from Chinese herbal medicine, Salvia miltiorrhiza Bunge. Herein, we evaluated whether Tan-I could enhance the efficacy of ovarian cancer to chemotherapy of Paclitaxel.
Ovarian cancer cells A2780 and ID-8 were exposed with Tan-I (4.8 µg/mL), Paclitaxel (0.1 µg/mL), or Tan-I combination with Paclitaxel for 24 hours. The cell proliferation was analyzed by CCK8 and EdU staining. Cell apoptosis was analyzed by the TUNEL assay and flow cytometry. The protein levels were determined by western blot. Cell migration was analyzed by Transwell and wound healing. Cell senescence was analyzed by senescence-associated b-galactosidase staining. Antitumor activity was analyzed by a subcutaneous tumor xenograft model of human ovarian cancer in nude mice. The protein expression and apoptosis level of tumor tissues were analyzed by immunohistochemistry and TUNEL staining.
Tan-I treatment significantly elevated the Paclitaxel-cause reduction of A2780 and ID-8 cell proliferation and cell migration. Tan-I combination with Paclitaxel promotes apoptosis of cancer cells by promoting Bax expression and Bcl-2 expression. Besides, Tan-I treatment can notably increase Paclitaxel-inducing cell senescence by promoting DNA damage and senescence-associated proteins such as p21 and p16. Furthermore, the result of the transplanted tumor model indicated that Tan-I combination with Paclitaxel could inhibit tumor growth in vivo by inhibiting cell proliferation and inducing cell apoptosis.
Natural compound Tan-I enhances the efficacy of ovarian cancer to Paclitaxel chemotherapy. The results will help to supply the potential clinical use of ovarian carcinoma cells.
紫杉醇是临床上广泛应用的卵巢癌一线化疗药物。丹参酮I（Tan-I）是从中药丹参中提取的重要脂溶性成分之一。在此，我们评估了Tan-I是否能增强卵巢癌对紫杉醇化疗的疗效。
将卵巢癌细胞A2780和ID-8分别用Tan-I（4.8μg/mL）、紫杉醇（0.1μg/mL）或Tan-I与紫杉醇联合处理24小时。通过CCK8和EdU染色分析细胞增殖情况。通过TUNEL检测和流式细胞术分析细胞凋亡情况。通过蛋白质印迹法测定蛋白质水平。通过Transwell和伤口愈合实验分析细胞迁移情况。通过衰老相关β-半乳糖苷酶染色分析细胞衰老情况。通过人卵巢癌裸鼠皮下肿瘤异种移植模型分析抗肿瘤活性。通过免疫组织化学和TUNEL染色分析肿瘤组织的蛋白质表达和凋亡水平。
Tan-I处理显著提高了紫杉醇导致的A2780和ID-8细胞增殖及细胞迁移的降低。Tan-I与紫杉醇联合通过促进Bax表达和降低Bcl-2表达来促进癌细胞凋亡。此外，Tan-I处理可通过促进DNA损伤以及衰老相关蛋白如p21和p16的表达，显著增强紫杉醇诱导的细胞衰老。此外，移植瘤模型结果表明，Tan-I与紫杉醇联合可通过抑制细胞增殖和诱导细胞凋亡来抑制体内肿瘤生长。
天然化合物Tan-I增强了卵巢癌对紫杉醇化疗的疗效。这些结果将有助于为卵巢癌细胞的潜在临床应用提供依据。
