Hu Jiudong, Hu Yujie, Zhang Xiangqi, Zhang Jingxian, Zhou Yangyun, Wang Xiaohe, Wu Wenhui, Chen Junjun, Han Yonglong
College of Food Science and Technology, Shanghai Ocean University, Shanghai, 201306, People's Republic of China.
Department of Pharmacy, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Xuhui, Shanghai, 200030, People's Republic of China.
J Nat Med. 2025 May;79(3):621-638. doi: 10.1007/s11418-025-01879-6. Epub 2025 Apr 8.
Ovarian cancer (OC) is the most common malignant gynecologic tumor, with the highest mortality rate among female reproductive system cancers. Resistance to chemotherapy drugs, which often develops after long-term use, is a major cause of treatment failure. In recent years, traditional Chinese medicine has been widely used in the treatment of tumor for their advantages in improving the efficacy of chemotherapy and alleviating the toxic side effects. Tenacissoside G (Tsd-G), as one of the main active ingredients of Marsdenia tenacissima, exhibits anti-tumor effects. However, its impact on ovarian cancer is not well understood. To assess the role and mechanism of Tsd-G in reversing paclitaxel (PTX) resistance, the reversal fold of Tsd-G in combination with PTX on OC PTX-resistant (A2780/T) cells was determined using CCK-8 assay. The apoptosis level and migration ability of A2780/T cells after 24 h treatment with Tsd-G and PTX were assessed by Hoechst 33,342, flow cytometry, and wound healing assay. Western Blot and Src overexpression plasmid were used to explore the relationship between Src and PTX resistance. The relationship between Src expression and human OC was analyzed by gene expression database. The effect of Tsd-G on P-gp activity was detected by flow cytometry. Western blot and RT-PCR experiments were performed to detect the differences in mRNA and protein expression of Src/PTN/P-gp signaling axis to validate the mechanism of Tsd-G in reversing the resistance to PTX in ovarian cancer. The results showed that Tsd-G reverses PTX resistance in ovarian cancer cells by regulating cell proliferation, cell cycle, inducing apoptosis, and inhibiting migration. The mechanism might associate with the inhibition of Src expression and phosphorylation activation, which in turn inhibits the expression and activity of downstream PTN and P-gp. This study provides a new idea for the treatment of PTX-resistant OC patients and provides theoretical support for revealing the anti-ovarian cancer active ingredients in Marsdenia tenacissima.
卵巢癌（OC）是最常见的妇科恶性肿瘤，在女性生殖系统癌症中死亡率最高。化疗药物耐药性通常在长期使用后出现，是治疗失败的主要原因。近年来，中药因其在提高化疗疗效和减轻毒副作用方面的优势而被广泛应用于肿瘤治疗。通关藤苷G（Tsd-G）作为通关藤的主要活性成分之一，具有抗肿瘤作用。然而，其对卵巢癌的影响尚不清楚。为了评估Tsd-G在逆转紫杉醇（PTX）耐药性中的作用和机制，采用CCK-8法测定Tsd-G联合PTX对OC PTX耐药（A2780/T）细胞的逆转倍数。通过Hoechst 33342、流式细胞术和伤口愈合试验评估Tsd-G和PTX处理24小时后A2780/T细胞的凋亡水平和迁移能力。采用蛋白质免疫印迹法和Src过表达质粒探讨Src与PTX耐药性的关系。通过基因表达数据库分析Src表达与人类OC的关系。采用流式细胞术检测Tsd-G对P-糖蛋白活性的影响。进行蛋白质免疫印迹和RT-PCR实验，检测Src/PTN/P-糖蛋白信号轴mRNA和蛋白表达的差异，以验证Tsd-G逆转卵巢癌对PTX耐药的机制。结果表明，Tsd-G通过调节细胞增殖、细胞周期、诱导凋亡和抑制迁移来逆转卵巢癌细胞的PTX耐药性。其机制可能与抑制Src表达和磷酸化激活有关，进而抑制下游PTN和P-糖蛋白的表达和活性。本研究为PTX耐药OC患者的治疗提供了新思路，为揭示通关藤抗卵巢癌活性成分提供了理论支持。
