Effects of sea cucumber polysaccharide regulating JAK2/STAT3/survivin pathway on proliferation and apoptosis of hepatocellular carcinoma cells_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 LU Zhanhui ^1,2 , BAI Yangqiu ³ , SUN Chenyi ⁴ , ZHANG Xiaofei ²

1. Department of Gastroenterology, General Hospital of Jinshui District of Zhengzhou (Teaching Hospital of Henan University of Science and Technology), Zhengzhou 450008, P. R. China;
2. Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P. R. China;
3. Department of Gastroenterology, Henan Provincial People’s Hospital, Zhengzhou 450003, P. R. China;
4. Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, P. R. China;

Corresponding?author：

LU Zhanhui, Email: 7885937@qq.com

Keywords：

sea cucumber polysaccharide; JAK2/STAT3/survivin pathway; HepG2 cell; proliferation; apoptosis

DOI：

10.7507/1007-9424.202109046

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To study the effects of sea cucumber polysaccharide (SCPS) on the proliferation and apoptosis of hepatocellular carcinoma (HCC) cells, and to explore its effect on JAK2/STAT3/survivin pathway. Methods The human HCC cell lines HepG2 were placed into 24-well plates after culturing to the logarithmic phase, then dealed with different concentrations (0, 50, 100, 200 μg/mL) of SCPS. The MTT assay was used to detect the effects of different concentrations of SCPS on cell proliferation at 12 h, 24 h, and 36 h. The effect of SCPS on cell apoptosis was analyzed by flow cytometry. The mRNA and protein expression levels of JAK2, STAT3, and survivin were detected by real-time quantitative PCR (qRT-PCR) and Western blot at 36 h after treatment with SCPS, respectively. Then, the human HepG2 cells treated with different concentrations (0, 50, 100, 200 μg/mL) of SCPS were subcutaneously xenografted into nude mice to observe the effect of SCPS on the growth of tumor tissues in nude mice. At the same time, the expressions of phosphorylated JAK2, STAT3, and survivin proteins in tumor tissues were detected by immunohistochemical method. Results After treatment with different concentrations of SCPS, the proliferation inhibition rate of HepG2 cells increased over time and increased SCPS concentrations (P<0.05). After 36 h cultivation time, the apoptosis rate of cells treated with different concentrations of SCPS was statistically significant (F=117.110, P<0.001) and increased with the increase of SCPS concentrations (P<0.05). The protein expression levels of JAK2, STAT3, survival and their phosphorylated proteins decreased gradually with the increase of SCPS concentrations (P<0.05), but there was no significant difference in the mRNA expression level (P>0.05). With the increase of SCPS concentration, the tumor volume of nude mice gradually reduced (P<0.05). At the same time, the results of immunohistochemical detection showed that the positive expression rates of phosphorylated JAK2, STAT3, and survivin proteins in tumor tissues decreased with the increase of SCPS concentrations (P<0.05). Conclusion From preliminary results of this study, SCPS could inhibit the proliferation of HCC cells and promote their apoptosis, which might be achieved by regulating the phosphorylated expressions of JAK2, STAT3, and survivin in the JAK2/STAT3/survivin pathway.

Citation： LU Zhanhui, BAI Yangqiu, SUN Chenyi, ZHANG Xiaofei. Effects of sea cucumber polysaccharide regulating JAK2/STAT3/survivin pathway on proliferation and apoptosis of hepatocellular carcinoma cells. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2022, 29(7): 875-880. doi: 10.7507/1007-9424.202109046 Copy

1.	Islami F, Miller KD, Siegel RL, et al. Disparities in liver cancer occurrence in the United States by race/ethnicity and state. CA Cancer J Clin, 2017, 67(4): 273-289.
2.	Hu ZQ, Lu Y, Cui D, et al. MicroRNAs and long non-coding RNAs in liver surgery: diagnostic and therapeutic merits. Hepatobiliary Pancreat Dis Int, 2020, 19(3): 218-228.
3.	Pérez-Herrero E, Fernández-Medarde A. Advanced targeted therapies in cancer: drug nanocarriers, the future of chemotherapy. Eur J Pharm Biopharm, 2015, 93: 52-79.
4.	Greten TF, Mauda-Havakuk M, Heinrich B, et al. Combined locoregional-immunotherapy for liver cancer. J Hepatol, 2019, 70(5): 999-1007.
5.	Yang Z, Zhang Q, Yu L, et al. The signaling pathways and targets of traditional Chinese medicine and natural medicine in triple-negative breast cancer. J Ethnopharmacol, 2021, 264: 113249. doi: 10.1016/j.jep.2020.113249.
6.	李天, 劉一帆, 江先漢, 等. 海參多糖抑制人腎癌細胞A498的生長轉移作用機制. 基因組學與應用生物學, 2020, 39(3): 1344-1350.
7.	Zhao Q, Liu ZD, Xue Y, et al. Ds-echinoside A, a new triterpene glycoside derived from sea cucumber, exhibits antimetastatic activity via the inhibition of NF-κB-dependent MMP-9 and VEGF expressions. J Zhejiang Univ Sci B, 2011, 12(7): 534-544.
8.	宋濤, 王艷麗, 楊雪, 等. siRNA沉默STAT3基因對肝癌細胞HepG2增殖的影響. 西安交通大學學報(醫學版), 2013, 34(2): 155-158, 172.
9.	Lu JW, Ho YJ, Yang YJ, et al. Zebrafish as a disease model for studying human hepatocellular carcinoma. World J Gastroenterol, 2015, 21(42): 12042-12058.
10.	Ohiwa T, Ebata T, Mizuno T, et al. Occult synchronous liver metastasis from perihilar cholangiocarcinoma. Surgery, 2019, 166(3): 290-296.
11.	Nio K, Yamashita T, Kaneko S. The evolving concept of liver cancer stem cells. Mol Cancer, 2017, 16(1): 4. doi: 10.1186/s12943-016-0572-9.
12.	Zhang Z, Tan X, Luo J, et al. The miR-30a-5p/CLCF1 axis regulates sorafenib resistance and aerobic glycolysis in hepatocellular carcinoma. Cell Death Dis, 2020, 11(10): 902. doi: 10.1038/s41419-020-03123-3.
13.	Ling CQ, Fan J, Lin HS, et al. Clinical practice guidelines for the treatment of primary liver cancer with integrative traditional Chinese and Western medicine. J Integr Med, 2018, 16(4): 236-248.
14.	韓慧敏, 謝安, 羅杰英. 海參多糖提取工藝研究. 當代中醫師, 2000, 16(1): 56-57.
15.	Amidi S, Hashemi Z, Motallebi A, et al, Sea cucumber extract plays an important role in the process of anti-cancer. Mar Drugs, 2017, 15(10): 314-328.
16.	Wang J, Han H, Chen X, et al. Cytotoxic and apoptosis-inducing activity of triterpene glycosides from Holothuria scabra and Cucumaria frondosa against HepG2 cells. Mar Drugs, 2014, 12(8): 4274-4290.
17.	Zhang ZH, Li MY, Wang Z, et al. Convallatoxin promotes apoptosis and inhibits proliferation and angiogenesis through crosstalk between JAK2/STAT3 (T705) and mTOR/STAT3 (S727) signaling pathways in colorectal cancer. Phytomedicine, 2020, 68: 153172. doi: 10.1016/j.phymed.2020.153172.
18.	魏薇, 唐祎, 代婧, 等. 鉤吻總堿通過JAK2/STAT3/Survivin通路調控人舌癌細胞株Tca8113增殖、凋亡的作用探討. 臨床和實驗醫學雜志, 2020, 19(2): 140-144.

1. Islami F, Miller KD, Siegel RL, et al. Disparities in liver cancer occurrence in the United States by race/ethnicity and state. CA Cancer J Clin, 2017, 67(4): 273-289.
2. Hu ZQ, Lu Y, Cui D, et al. MicroRNAs and long non-coding RNAs in liver surgery: diagnostic and therapeutic merits. Hepatobiliary Pancreat Dis Int, 2020, 19(3): 218-228.
3. Pérez-Herrero E, Fernández-Medarde A. Advanced targeted therapies in cancer: drug nanocarriers, the future of chemotherapy. Eur J Pharm Biopharm, 2015, 93: 52-79.
4. Greten TF, Mauda-Havakuk M, Heinrich B, et al. Combined locoregional-immunotherapy for liver cancer. J Hepatol, 2019, 70(5): 999-1007.
5. Yang Z, Zhang Q, Yu L, et al. The signaling pathways and targets of traditional Chinese medicine and natural medicine in triple-negative breast cancer. J Ethnopharmacol, 2021, 264: 113249. doi: 10.1016/j.jep.2020.113249.
6. 李天, 劉一帆, 江先漢, 等. 海參多糖抑制人腎癌細胞A498的生長轉移作用機制. 基因組學與應用生物學, 2020, 39(3): 1344-1350.
7. Zhao Q, Liu ZD, Xue Y, et al. Ds-echinoside A, a new triterpene glycoside derived from sea cucumber, exhibits antimetastatic activity via the inhibition of NF-κB-dependent MMP-9 and VEGF expressions. J Zhejiang Univ Sci B, 2011, 12(7): 534-544.
8. 宋濤, 王艷麗, 楊雪, 等. siRNA沉默STAT3基因對肝癌細胞HepG2增殖的影響. 西安交通大學學報(醫學版), 2013, 34(2): 155-158, 172.
9. Lu JW, Ho YJ, Yang YJ, et al. Zebrafish as a disease model for studying human hepatocellular carcinoma. World J Gastroenterol, 2015, 21(42): 12042-12058.
10. Ohiwa T, Ebata T, Mizuno T, et al. Occult synchronous liver metastasis from perihilar cholangiocarcinoma. Surgery, 2019, 166(3): 290-296.
11. Nio K, Yamashita T, Kaneko S. The evolving concept of liver cancer stem cells. Mol Cancer, 2017, 16(1): 4. doi: 10.1186/s12943-016-0572-9.
12. Zhang Z, Tan X, Luo J, et al. The miR-30a-5p/CLCF1 axis regulates sorafenib resistance and aerobic glycolysis in hepatocellular carcinoma. Cell Death Dis, 2020, 11(10): 902. doi: 10.1038/s41419-020-03123-3.
13. Ling CQ, Fan J, Lin HS, et al. Clinical practice guidelines for the treatment of primary liver cancer with integrative traditional Chinese and Western medicine. J Integr Med, 2018, 16(4): 236-248.
14. 韓慧敏, 謝安, 羅杰英. 海參多糖提取工藝研究. 當代中醫師, 2000, 16(1): 56-57.
15. Amidi S, Hashemi Z, Motallebi A, et al, Sea cucumber extract plays an important role in the process of anti-cancer. Mar Drugs, 2017, 15(10): 314-328.
16. Wang J, Han H, Chen X, et al. Cytotoxic and apoptosis-inducing activity of triterpene glycosides from Holothuria scabra and Cucumaria frondosa against HepG2 cells. Mar Drugs, 2014, 12(8): 4274-4290.
17. Zhang ZH, Li MY, Wang Z, et al. Convallatoxin promotes apoptosis and inhibits proliferation and angiogenesis through crosstalk between JAK2/STAT3 (T705) and mTOR/STAT3 (S727) signaling pathways in colorectal cancer. Phytomedicine, 2020, 68: 153172. doi: 10.1016/j.phymed.2020.153172.
18. 魏薇, 唐祎, 代婧, 等. 鉤吻總堿通過JAK2/STAT3/Survivin通路調控人舌癌細胞株Tca8113增殖、凋亡的作用探討. 臨床和實驗醫學雜志, 2020, 19(2): 140-144.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effects of sea cucumber polysaccharide regulating JAK2/STAT3/survivin pathway on proliferation and apoptosis of hepatocellular carcinoma cells

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content