Inhibitory effect of curcumin on human carcinoma SMMC-7721 cells xenografted in nude mice and its mechanism
SUN Jun 1,2, XU Wei 2,3, LU Rongzhu 2,4, ZHU Xiaoren 2, XU Xinming 1, JIANG Yiquan 1,2, CHEN Jian 1,2
（1. Department of Hepatobiliary Surgery, Kunshan Hospital Affiliated to Jiangsu University, Suzhou Jiangsu 215300；2. School of Medicine, Jiangsu University, Zhenjiang Jiangsu 212013； 3. Department of Pathology, Yancheng Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Yancheng Jiangsu 224001; 4. Center for Experimental Research, Kunshan Hospital Affiliated to Jiangsu University, Suzhou Jiangsu 215300, China）
Abstract：Objective: To investigate the inhibitory effect of curcumin on the growth of human carcinoma SMMC-7721 cell transplanted tumor in nude mice and its potential mechanism. Methods: Transplanted tumor model of SMMC-7721 cells was established in 20 nude mice, and the tumorbearing nude mice were equally divided into control group and three different concentrations of curcumin （10, 50 and 100 mg/kg） groups, with 5 mice in each group. The mice in each group was intraperitoneally injected with normal saline or corresponding dose of curcumin, once a day, 200 μL each time, for 16 consecutive days. The body weight and tumor volume of each group were observed and recorded every other day from the day of administration. After 16 days, tumor tissues were harvested and tumor inhibition rates of curcumin treatment groups were calculated by the weighed tumor body. The expression levels of ER stress-related proteins and apoptotic proteins in tumor tissues were analyzed by Western blotting. The positive expressions of glucose requlated protein 78 （GRP78） and inositol requiring enzyme 1 （IRE1） were analyzed by immunohistochemical staining. Results: Compared with that in the control group, there was no significant difference in the weight gain of nude mice in different doses of curcumin groups （P>0.05）, whereas the volume of transplanted tumor in 50 and 100 mg/kg curcumin groups was significantly smaller than that in the control group and 10 mg/kg curcumin group（P<0.05）. The tumor inhibition rates of 10, 50 and 100 mg/kgcurcumin groups were 35.3%, 45.7% and 54.7%, respectively. Western blotting showed that GRP78, IRE1, C/EBP homologous protein （CHOP） and Cleaved caspase-3 protein expressions in 50 and 100 mg/kg curcumin groups were significantly up-regulated compared with that in the control group, and the protein expressions of p-PERK, p-eIF2α and Bcl-2 in 10, 50 and 100 mg/kg curcumin groups were higher than those in the control group （both P<0.05）. Results of immunohistochemical staining showed that the positive expression of proteins GRP78 and IRE1 in tumor tissues of all curcumin groups were markedly increased compared with the control group（all P<0.05）. Conclusion: Curcumin could inhibit the growth of subcutaneous transplanted tumor in nude mice with human hepatoma SMMC-7721 cells, which may be attributed to activating endoplasmic reticulum stress.
［Key words］curcumin; hepatocellular carcinoma cell; endoplasmic reticulum stress; unfolded protein reaction; apoptosis
孙俊, 徐伟, 陆荣柱, 等.. 姜黄素对人肝癌SMMC-7721细胞裸鼠移植瘤的抑制作用及其机制[J]. 江苏大学学报:医学版, 2022, 32(03): 219-225，230.
SUN Jun, XU Wei, LU Rongzhu,et al.. Inhibitory effect of curcumin on human carcinoma SMMC-7721 cells xenografted in nude mice and its mechanism. Journal of Jiangsu University(Medicine Edition), 2022, 32(03): 219-225，230.
