Wang Ling, Miao Yali, Wen Jirui, Cheng Juan, Wen Qiao, Zhao Zhiwei, Wu Jiang
Deep Underground Space Medical Center, West China Hospital, Sichuan University, Chengdu, China.
Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu, China.
Transl Cancer Res. 2023 Apr 28;12(4):828-836. doi: 10.21037/tcr-22-2240. Epub 2023 Mar 27.
Globally, ovarian cancer is the leading cause of female reproductive-related death, with a 5-year survival rate below 50%. Conventional therapies, such as cancer cell reduction and paclitaxel chemotherapy, have strong toxicity and are prone to drug resistance. Thus, the development of alternatives for the treatment of ovarian cancer is urgently needed. Methyl vanillate is a principal component of Thunberg. It is known that several cancer cells are inhibited by methyl vanillate; however, whether methyl vanillate can inhibit the proliferation and migration of ovarian cancer cells still needs to be further studied.
In this study, cell counting kit 8 (CCK8) was used to examine the effects of methyl vanillic acid on the proliferation of SKOV3 cell lines and human ovarian surface epithelial cell (HOSEpiC) lines. Wound healing and transwell assays were used to determine the effect of methyl vanillate on cell migration. The expression of epithelial-mesenchymal transition (EMT) marker proteins (E-cadherin and vimentin), transcription factors (Snail and ZEB2), and skeletal proteins (F-actin) were evaluated with Western blotting. F-actin was detected by immunofluorescence assay.
The proliferation and migration of SKOV3 cells were dose-dependently inhibited by methyl vanillate, but HOSEpiC cells were not inhibited by low concentrations of methyl vanillate. Western blotting analyses revealed a significant decrease in the expression of vimentin and a significant increase in the expression of E-cadherin in SKOV3 cells treated with methyl vanillate. This finding indicated that EMT inhibition was induced by the vanillate. Furthermore, methyl vanillate inhibited the expression of transcription factors (Snail and ZEB2) in SKOV3 cells as well as cytoskeletal F-actin assembly.
Methyl vanillate plays an important role in inhibiting EMT and cell proliferation and the migration of ovarian cancer, likely via the inhibition of the ZEB2/Snail signaling pathway. Consequently, methyl vanillate may be a promising therapeutic drug for ovarian cancer.
在全球范围内，卵巢癌是女性生殖相关死亡的主要原因，其5年生存率低于50%。传统疗法，如肿瘤细胞减灭术和紫杉醇化疗，毒性较强且易产生耐药性。因此，迫切需要开发治疗卵巢癌的替代方法。香草酸甲酯是山黧豆的主要成分。已知几种癌细胞会受到香草酸甲酯的抑制；然而，香草酸甲酯是否能抑制卵巢癌细胞的增殖和迁移仍有待进一步研究。
在本研究中，使用细胞计数试剂盒8（CCK8）检测香草酸对SKOV3细胞系和人卵巢表面上皮细胞（HOSEpiC）系增殖的影响。采用伤口愈合实验和Transwell实验来确定香草酸甲酯对细胞迁移的影响。通过蛋白质免疫印迹法评估上皮-间质转化（EMT）标志物蛋白（E-钙黏蛋白和波形蛋白）、转录因子（Snail和ZEB2）以及骨架蛋白（F-肌动蛋白）的表达。通过免疫荧光实验检测F-肌动蛋白。
香草酸甲酯剂量依赖性地抑制SKOV3细胞的增殖和迁移，但低浓度的香草酸甲酯对HOSEpiC细胞没有抑制作用。蛋白质免疫印迹分析显示，用香草酸甲酯处理的SKOV3细胞中波形蛋白的表达显著降低，E-钙黏蛋白的表达显著增加。这一发现表明香草酸甲酯可诱导EMT抑制。此外，香草酸甲酯抑制SKOV3细胞中转录因子（Snail和ZEB2）的表达以及细胞骨架F-肌动蛋白的组装。
香草酸甲酯可能通过抑制ZEB2/Snail信号通路，在抑制EMT以及卵巢癌细胞的增殖和迁移中发挥重要作用。因此，香草酸甲酯可能是一种有前景的卵巢癌治疗药物。
