Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, 100026, People's Republic of China.
Division of Gynecologic Oncology, University of North Carolina at Chapel Hill, 170 Manning Dr, Chapel Hill, NC, 27599, USA.
J Cancer Res Clin Oncol. 2023 Jul;149(7):3871-3883. doi: 10.1007/s00432-022-04276-8. Epub 2022 Aug 25.
Although paclitaxel is a promising first-line chemotherapeutic drug for ovarian cancer, acquired resistance to paclitaxel is one of the leading causes of treatment failure, limiting its clinical application. Asparagus officinalis has been shown to have anti-tumorigenic effects on cell growth, apoptosis, cellular stress and invasion of various types of cancer cells and has also been shown to synergize with paclitaxel to inhibit cell proliferation in ovarian cancer.
Human ovarian cancer cell lines MES and its PTX-resistant counterpart MES-TP cell lines were used and were treated with Asparagus officinalis and paclitaxel alone as well as in combination. Cell proliferation, cellular stress, invasion and DMA damage were investigated and the synergistic effect of a combined therapy analyzed.
In this study, we found that Asparagus officinalis combined with low-dose paclitaxel synergistically inhibited cell proliferation, induced cellular stress and apoptosis and reduced cell invasion in paclitaxel-sensitive and -resistant ovarian cancer cell lines. The combined treatment effects were dependent on DNA damage pathways and suppressing microtubule dynamics, and the AKT/mTOR pathway and microtubule-associated proteins regulated the inhibitory effect through different mechanisms in paclitaxel-sensitive and -resistant cells.
These findings suggest that the combination of Asparagus officinalis and paclitaxel have potential clinical implications for development as a novel ovarian cancer treatment strategy.
紫杉醇是卵巢癌有前途的一线化疗药物,但对紫杉醇的获得性耐药是治疗失败的主要原因之一,限制了其临床应用。研究表明,芦笋对多种癌细胞的生长、凋亡、细胞应激和侵袭具有抗肿瘤作用,并且还与紫杉醇协同抑制卵巢癌细胞的增殖。
使用人卵巢癌细胞系 MES 及其紫杉醇耐药对应物 MES-TP 细胞系,并单独和联合使用芦笋和紫杉醇进行处理。研究细胞增殖、细胞应激、侵袭和 DNA 损伤,并分析联合治疗的协同作用。
在这项研究中,我们发现芦笋与低剂量紫杉醇联合使用可协同抑制紫杉醇敏感和耐药卵巢癌细胞系的细胞增殖,诱导细胞应激和凋亡,并降低细胞侵袭。联合治疗效果依赖于 DNA 损伤途径和抑制微管动力学,AKT/mTOR 途径和微管相关蛋白通过不同的机制在紫杉醇敏感和耐药细胞中调节抑制作用。
这些发现表明,芦笋和紫杉醇的联合应用具有作为新型卵巢癌治疗策略的潜在临床意义。