Study of inhibitory effect of formononetin on human renal carcinoma cell 786-O and its mechanism
CHEN Qing1 LI Haihong2 OU Weining1 ZHANG Xing3
1.Department of Nephrology, the Second People’s Hospital of Yulin, Guangxi Zhuang Autonomous Region, Yulin 537000, China;
2.Department of Quality Control, the First People’s Hospital of Yulin, Guangxi Zhuang Autonomous Region, Yulin 537000, China;
3.Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guangxi Zhuang Autonomous Region, Guilin 541100, China
Abstract:Objective To observe the inhibitory effect of formononetin on human renal carcinoma cell 786-O and its mechanism. Methods Human renal carcinoma cell 786-O cultured with different doses of formononetin. They were divided into control group (0 μmol/L, group A), formononetin low-dose group (20 μmol/L, group B), formononetin medium-dose group (40 μmol/L, group C), and formononetin high-dose group (80 μmol/L, group D) according to drug dose. CCK8 method was used to detect the proliferation of four group; apoptosis was detected by flow cytometry and Hoechst staining; the expression of miR-155 was detected by RT-PCR; the protein expressions of P-PI3K and P-AKT were detected by Western blot. Results After 72 h of culture, the inhibitory rate of cell proliferation in groups B, C and D were higher than those in 24 and 48 h of culture. After 48 h of culture, the inhibitory rate of cell proliferation in groups B, C and D were higher than those in 24 h of culture, and the differences were statistically significant (all P < 0.05). After 24, 48 and 72 h of culture, the inhibitory rate of cell proliferation in groups B, C and D were higher than those in group A; groups C and D were higher than that in group B; and group D was higher than that in group C, and the differences were statistically significant (all P < 0.05). The apoptosis rate of four groups were statistically significant (P < 0.05). In group B, C and D, cell shrinkage and nucleus were observed, and the higher the drug dose was, the more obvious the cell apoptosis was; the nucleus of group A was complete and full in morphology. The expression of miR-155 level and P-PI3K and P-AKT proteins levels in groups B, C and D were lower than those in group A, the expression miR-155 level and P-PI3K and P-AKT proteins levels in groups C and D were lower than those in group B, and the expression miR-155 level and P-PI3K and P-AKT proteins levels in group D was lower than that in group C, and the differences were statistically significant (all P < 0.05). Conclusion Formononetin can significantly inhibit proliferation and induce apoptosis in human renal carcinoma cell 786-O, and the mechanism may be related to the down-regulation of miR-155 expression to inhibit the activation of PI3K/AKT signaling pathway.
陈庆1 李海虹2 欧伟宁1 张幸3. 芒柄花黄素对人肾癌细胞786-O的抑制作用及机制研究[J]. 中国医药导报, 2021, 18(12): 11-15,19.
CHEN Qing1 LI Haihong2 OU Weining1 ZHANG Xing3. Study of inhibitory effect of formononetin on human renal carcinoma cell 786-O and its mechanism. 中国医药导报, 2021, 18(12): 11-15,19.
[1] Li X,Yin A,Zhang W,et al. Jam3 Promotes Migration and Suppresses Apoptosis of Renal Carcinoma Cell Lines [J]. Int J Mol Med,2018,42(5):2923-2929.
[2] Capitanio U,Montorsi F. Renal cancer [J]. Lancet,2016, 387(10021):894-906.
[3] Yao JN,Zhang XX,Zhang YZ,et al. Discovery and anticancer evaluation of a formononetin derivative against gastric cancer SGC7901 cells [J]. Invest New Drugs,2019, 37(6):1300-1308.
[4] Zhang J,Liu LK,Wang J,et al. Formononetin,an isoflavone from Astragalus membranaceus inhibits proliferation and metastasis of ovarian cancer cells[J]. J Ethnopharmacol,2018,221:91-99.
[5] 柳青,梁梅花,张幸,等.芒柄花黄素对人膀胱癌细胞T739增殖、凋亡的影响及机制探讨[J].中国医药导报,2017,14(25):4-7.
[6] Sánchez-Gastaldo A,Kempf E,Alba AG,et al. Systemic treatment of renal cell cancer:A comprehensive review [J]. Cancer Treat Rev,2017,60:77-89.
[7] Bacolod MD,Barany F,Pilones K,et al. Chapter Four-Pathways-and epigenetic-based assessment of relative immune infiltration in various types of solid tumors [J]. Adv Cancer Res,2019,142:107-143.
[8] Wang D,Xiao ZJ,Shou JZ,et al. Clinical analysis of 8 cases of the mixed epithelial and stromal tumour family of kidney [J]. Zhonghua Yi Xue Za Zhi,2019,99(10):771-774.
[9] Park S,Bazer FW,Lim W,et al. The O-methylated isoflavone,formononetin,inhibits human ovarian cancer cell proliferation by sub G0/G1 cell phase arrest through PI3K/AKT and ERK1/2 inactivation [J]. J Cell Biochem,2018,119(9):7377-7387.
[10] Xin M,Wang Y,Ren Q,et al. Formononetin and metformin act synergistically to inhibit growth of MCF-7 breast cancer cells in vitro [J]. Biomed Pharmacother,2019,109:2084-2089.
[11] Tay KC,Tan LT,Chan CK,et al. Formononetin: A Review of Its Anticancer Potentials and Mechanisms [J]. Front Pharmacol,2019,10:820.
[12] Zhang K,Wang YW,Wang YY,et al. Identification of microRNA biomarkers in the blood of breast cancer patients based on microRNA profiling [J]. Gene,2017,619:10-20.
[13] Dudics S,Venkatesha SH,Moudgil KD. The micro-RNA expression profiles of autoimmune arthritis reveal novel biomarkers of the disease and therapeutic response [J]. Int J Mol Sci,2018,19(18):2293.
[14] McGeary SE,Lin KS,Shi CY,et al. The biochemical basis of microRNA targeting efficacy [J]. Science,2019, 366(6472):eaav1741.
[15] Dragomir MP,Knutsen E,Calin GA. SnapShot:Unconventional miRNA Functions [J]. Cell,2018,174(4):1038-1038.e1.
[16] Shahid S,Kim G,Johnson NR,et al. MicroRNAs from the parasitic plant Guscuta campestris target host messenger RNAs [J]. Nature,2018,553(7686):82-85.
[17] Hines PJ. MicroRNAs in functional and dysfunctional pain [J]. Science,2017,356(6343):1134-1136.
[18] Sambandan S,Akbalik G,Kochen L,et al. Activity-dependent spatially localized miRNA maturation in neuronal dendrites [J]. Science,2017,355(6325):634-637.
[19] Cao H,Huang S,Liu A,et al. Up-regulated expression of miR-155 in human colonic cancer [J]. J Cancer Res Ther,2018,14(3):604-607.
[20] Chen L,Yang X,Zhao J,et al. Circ_0008532 promotes bladder cancer progression by regulation of the miR-155-5p/miR-330-5p/MTGR1 axis [J]. J Exp Clin Cancer Res,2020,39(1):94.
[21] Shao C,Yang F,Qin Z,et al. The value of miR-155 as a biomarker for the diagnosis and prognosis of lung cancer:a systematic review with meta-analysis [J]. BMC Cancer,2019,19(1):1103.
[22] Santos JC,Lima NDS,Sarian LO,et al. Exosome-mediated breast cancer chemoresistance via miR-155 transfer [J]. Sci Rep,2018,8(1):829.
[23] Tao M,Zhou Y,Jin Y,et al. Blocking lncRNA MIR155HG/miR-155-5p/-3p inhibits proliferation,invasion and migration of clear cell renal cell carcinoma [J]. Pathol Res Pract,2020,216(2):152803.
[24] Yan Y,Huang H. Interplay Among PI3K/AKT,PTEN/FOXO and AR Signaling in Prostate Cancer [J]. Adv Exp Med Biol,2019,1210:319-331.
[25] Costa RLB,Han HS,Gradishar WJ. Targeting the PI3K/AKT/mTOR pathway in triple-negative breast cancer:A review [J]. Breast Cancer Res Treat,2018,169(3):397-406.
[26] Han B,Wang S,Zhao H. MicroRNA-21 and microRNA-155 Promote the Progression of Burkitt’s Lymphoma by the PI3K/AKT Signaling Pathway [J]. Int J Clin Exp Pathol,2020,13(1):89-98.