Wang Yue, Li Ying, Wang Liang, Chen Buze, Zhu Miaolin, Ma Chunyi, Mu Chunyan, Tao Aibin, Li Shibao, Luo Lan, Ma Ping, Ji Shuai, Lan Ting
Xuzhou Key Laboratory of Laboratory Diagnostics, Xuzhou Medical University, Xuzhou, China.
School of Medical Technology, Xuzhou Medical University, Xuzhou, China.
Front Pharmacol. 2022 May 12;13:779608. doi: 10.3389/fphar.2022.779608. eCollection 2022.
Ovarian cancer is one of the most common gynecological malignancies in women worldwide with a poor survival rate. Cinnamaldehyde (CA), a bioactive substance isolated from cinnamon bark, is a natural drug and has shown that it can inhibit the progression of other tumors. However, the role of CA in ovarian cancer and its mechanism is poorly understood. In this study, wound healing assays, plate cloning, CCK-8, and transwell assays were used to determine cell proliferation and invasion. Western blot and flow cytometry were used to detect apoptosis levels. Western blot and immunofluorescence were used to detect changes in cellular EMT levels. The Western blot was used to detect levels of the PI3K/AKT signaling pathway. , we established a subcutaneous transplantation tumor model in nude mice to verify the role of CA in the progression and metastasis of ovarian cancer. Our data showed that CA was able to inhibit the cell viability of ovarian cancer. The results of scratch assay and transwell assay also showed that CA inhibited the proliferation and invasion ability of A2780 and SKOV3 cells. In addition, CA promoted apoptosis by increasing the expression of cleaved-PARP and cleaved-caspase 3 in ovarian cancer cells. Mechanistically, we found that CA inhibited the EGF-induced PI3K/AKT signaling pathway and reduced the phosphorylation levels of mTOR, PI3K, and AKT. The EGF-induced EMT process was also abolished by CA. The EMT process induced by AKT-specific activator SC79 was also suppressed by CA. Furthermore, in , CA significantly repressed the progression of ovarian cancer as well as liver metastasis. In all, our results suggest that CA inhibits ovarian cancer progression and metastasis and and inhibits EGF-induced EMT processes through the PI3K/AKT signaling pathway.
卵巢癌是全球女性中最常见的妇科恶性肿瘤之一,生存率较低。肉桂醛(CA)是从肉桂树皮中分离出的一种生物活性物质,是一种天然药物,已显示出它可以抑制其他肿瘤的进展。然而,CA在卵巢癌中的作用及其机制尚不清楚。在本研究中,采用伤口愈合试验、平板克隆、CCK-8和Transwell试验来确定细胞增殖和侵袭情况。采用蛋白质免疫印迹法和流式细胞术检测细胞凋亡水平。采用蛋白质免疫印迹法和免疫荧光法检测细胞上皮-间质转化(EMT)水平的变化。采用蛋白质免疫印迹法检测PI3K/AKT信号通路的水平。此外,我们在裸鼠中建立了皮下移植瘤模型,以验证CA在卵巢癌进展和转移中的作用。我们的数据表明,CA能够抑制卵巢癌细胞的活力。划痕试验和Transwell试验的结果还表明,CA抑制了A2780和SKOV3细胞的增殖和侵袭能力。此外,CA通过增加卵巢癌细胞中裂解的PARP和裂解的半胱天冬酶3的表达来促进细胞凋亡。从机制上讲,我们发现CA抑制了表皮生长因子(EGF)诱导的PI3K/AKT信号通路,并降低了雷帕霉素靶蛋白(mTOR)、PI3K和AKT的磷酸化水平。CA还消除了EGF诱导的EMT过程。CA也抑制了AKT特异性激活剂SC79诱导的EMT过程。此外,在体内,CA显著抑制了卵巢癌的进展以及肝转移。总之,我们的结果表明,CA通过PI3K/AKT信号通路抑制卵巢癌的进展和转移,并抑制EGF诱导的EMT过程。