ADAM17-shRNA promotes apoptosis of HT29 colon cancer cells through Akt/GSK3β signaling pathway_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHANG Qi , YANG Guanghua , LIU Shaopeng , ZHANG Guozhi ,  WANG Changyou

Department of General Surgery, Affiliated Hospital of North China University of Science and Technology, Tangshan, Hebei 063000, P. R. China;

Corresponding author：

WANG Changyou, Email: fhbj-2004@163.com

Keywords：

disintegrin and metalloproteinase 17; colon cancer; protein kinase B; glycogen synthase kinase-3β; apoptosis

DOI：

10.7507/1007-9424.201710044

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the inhibition effect of silence of a disintegrin and metalloproteinase 17 (ADAM17) gene on proliferation and apoptosis of HT29 colon cancer cells and its possible mechanism. Methods HT29cells were divided into 3 groups: cells of interference group were transfected with recombinant lentivirus vector, cells of negative control group were transfected with negative recombinant lentivirus vector, and cells of blank control group were treated with PBS. The expression of ADAM17 mRNA was detected by real-time PCR, the expressions of ADAM17 protein, caspase3, protein kinase B (Akt), glycogen synthase kinase-3β (GSK3β), phospho-protein kinase B (P-Akt), phospho-glycogen synthase kinase-3β (P-GSK3β) protein were detected by Western blot method, the cell proliferation was detected by MTT assay, and the apoptosis rate was detected by Annexin V-FITC/PI cell death detection kit. Results Compared with the control group and the negative control group, the interference group was related to low expressions of ADAM17 mRNA and its protein, low optical density value at the same time point (24, 48, and 72 h), high apoptosis rate, high expression level of caspase3 protein, but low expression levels of P-Akt and P-GSK3β protein (P<0.05). Conclusion Silent ADAM17 gene could significantly induces apoptosis and inhibits the proliferation of HT29 cells, which maybe via inhibiting Akt/GSK3β signaling pathway.

Citation： ZHANG Qi, YANG Guanghua, LIU Shaopeng, ZHANG Guozhi, WANG Changyou. ADAM17-shRNA promotes apoptosis of HT29 colon cancer cells through Akt/GSK3β signaling pathway. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2018, 25(5): 534-539. doi: 10.7507/1007-9424.201710044 Copy

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4.	Narita D, Seclaman E, Ursoniu S, et al. Increased expression of ADAM12 and ADAM17 genes in laser-capture microdissected breast cancers and correlations with clinical and pathological characteristics. Acta Histochem, 2012, 114(2): 131-139.
5.	Xu M, Zhou H, Zhang C, et al. ADAM17 promotes epithelial-mesenchymal transition via TGF-β/Smad pathway in gastric carcinoma cells. Int J Oncol, 2016, 49(6): 2520-2528.
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9.	Shen H, Li L, Zhou S, et al. The role of ADAM17 in tumorigenesis and progression of breast cancer. Tumour Biol, 2016, [Epub ahead of print].
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13.	Dosch J, Ziemke E, Wan S, et al. Targeting ADAM17 inhibits human colorectal adenocarcinoma progression and tumor-initiating cell frequency. Oncotarget, 2017, 8(39): 65090-65099.
14.	Wang XJ, Feng CW, Li M. ADAM17 mediates hypoxia-induced drug resistance in hepatocellular carcinoma cells through activation of EGFR/PI3K/Akt pathway. Mol Cell Biochem, 2013, 380(1-2): 57-66.
15.	Muñoz-Pinedo C. Signaling pathways that regulate life and cell death: evolution of apoptosis in the context of self-defense. Adv Exp Med Biol, 2012, 738: 124-143.
16.	Visconti R, D'Adamio L. Functional cloning of genes regulating apoptosis in neuronal cells. Methods Mol Biol, 2007, 399: 125-131.
17.	张乙川, 刘峰, 王俊, 等. 雷公藤红素诱导人肝癌SMMC-7721细胞凋亡研究. 中国普外基础与临床杂志, 2016, 23(1): 48-51.
18.	Hawley SA, Ross FA, Gowans GJ, et al. Phosphorylation by Akt within the ST loop of AMPK-α1 down-regulates its activation in tumour cells. Biochem J, 2014, 459(2): 275-287.
19.	殷舞, 钟晓刚, 黄顺荣, 等. PI3K/Akt/mTOR信号通路在大肠腺瘤恶性转化中的表达及意义. 广东医学, 2013, 34(2): 238-240.
20.	Meng X, Hu B, Hossain MM, et al. ADAM17-siRNA inhibits MCF-7 breast cancer through EGFR-PI3K-AKT activation. Int J Oncol, 2016, 49(2): 682-690.
21.	涂业桃, 舒静, 田文林, 等. 下调血管生成素基因表达对膀胱癌移植瘤生长及p-AKT、p-GSK3β、p-mTOR表达的影响. 广东医学, 2015, 36(4): 501-504.
22.	Chiara F, Rasola A. GSK-3 and mitochondria in cancer cells. Front Oncol, 2013, 3: 16.
23.	Jin Z, Cheng X, Feng H, et al. Apatinib inhibits angiogenesis via suppressing Akt/GSK3β/ANG signaling pathway in anaplastic thyroid cancer. Cell Physiol Biochem, 2017, 44(4): 1471-1484.
24.	Liu RM, Sun DN, Jiao YL, et al. Macrophage migration inhibitory factor promotes tumor aggressiveness of esophageal squamous cell carcinoma via activation of Akt and inactivation of GSK3β. Cancer Lett, 2018, 412: 289-296.
25.	Sokolosky M, Chappell WH, Stadelman K, et al. Inhibition of GSK-3β activity can result in drug and hormonal resistance and alter sensitivity to targeted therapy in MCF-7 breast cancer cells. Cell Cycle, 2014, 13(5): 820-833.

1. Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2): 115-132.
2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin, 2017, 67(1): 7-30.
3. Mullooly M, McGowan PM, Crown J, et al. The ADAMs family of proteases as targets for the treatment of cancer. Cancer Biol Ther, 2016, 17(8): 870-880.
4. Narita D, Seclaman E, Ursoniu S, et al. Increased expression of ADAM12 and ADAM17 genes in laser-capture microdissected breast cancers and correlations with clinical and pathological characteristics. Acta Histochem, 2012, 114(2): 131-139.
5. Xu M, Zhou H, Zhang C, et al. ADAM17 promotes epithelial-mesenchymal transition via TGF-β/Smad pathway in gastric carcinoma cells. Int J Oncol, 2016, 49(6): 2520-2528.
6. Vargas AJ, Thompson PA. Diet and nutrient factors in colorectal cancer risk. Nutr Clin Pract, 2012, 27(5): 613-623.
7. Cheng CJ, Bahal R, Babar IA, et al. MicroRNA silencing for cancer therapy targeted to the tumour microenvironment. Nature, 2015, 518(7537): 107-110.
8. Oikawa H, Maesawa C, Tatemichi Y, et al. A disintegrin and metalloproteinase 17(ADAM17) mediates epidermal growth factor receptor transactivation by angiotensinⅡ on hepatic stellate cells. Life Sci, 2014, 97(2): 137-144.
9. Shen H, Li L, Zhou S, et al. The role of ADAM17 in tumorigenesis and progression of breast cancer. Tumour Biol, 2016, [Epub ahead of print].
10. Rios-Doria J, Sabol D, Chesebrough J, et al. A Monoclonal antibody to ADAM17 inhibits tumor growth by inhibiting EGFR and non-EGFR-mediated pathways. Mol Cancer Ther, 2015, 14(7): 1637-1649.
11. 方文胜. 去整合素-金属蛋白酶17在结直肠腺瘤和癌中的表达及临床意义. 天津: 天津医科大学, 2012.
12. Groot AJ, Cobzaru C, Weber S, et al. Epidermal ADAM17 is dispensable for notch activation. J Invest Dermatol, 2013, 133(9): 2286-2288.
13. Dosch J, Ziemke E, Wan S, et al. Targeting ADAM17 inhibits human colorectal adenocarcinoma progression and tumor-initiating cell frequency. Oncotarget, 2017, 8(39): 65090-65099.
14. Wang XJ, Feng CW, Li M. ADAM17 mediates hypoxia-induced drug resistance in hepatocellular carcinoma cells through activation of EGFR/PI3K/Akt pathway. Mol Cell Biochem, 2013, 380(1-2): 57-66.
15. Muñoz-Pinedo C. Signaling pathways that regulate life and cell death: evolution of apoptosis in the context of self-defense. Adv Exp Med Biol, 2012, 738: 124-143.
16. Visconti R, D'Adamio L. Functional cloning of genes regulating apoptosis in neuronal cells. Methods Mol Biol, 2007, 399: 125-131.
17. 张乙川, 刘峰, 王俊, 等. 雷公藤红素诱导人肝癌SMMC-7721细胞凋亡研究. 中国普外基础与临床杂志, 2016, 23(1): 48-51.
18. Hawley SA, Ross FA, Gowans GJ, et al. Phosphorylation by Akt within the ST loop of AMPK-α1 down-regulates its activation in tumour cells. Biochem J, 2014, 459(2): 275-287.
19. 殷舞, 钟晓刚, 黄顺荣, 等. PI3K/Akt/mTOR信号通路在大肠腺瘤恶性转化中的表达及意义. 广东医学, 2013, 34(2): 238-240.
20. Meng X, Hu B, Hossain MM, et al. ADAM17-siRNA inhibits MCF-7 breast cancer through EGFR-PI3K-AKT activation. Int J Oncol, 2016, 49(2): 682-690.
21. 涂业桃, 舒静, 田文林, 等. 下调血管生成素基因表达对膀胱癌移植瘤生长及p-AKT、p-GSK3β、p-mTOR表达的影响. 广东医学, 2015, 36(4): 501-504.
22. Chiara F, Rasola A. GSK-3 and mitochondria in cancer cells. Front Oncol, 2013, 3: 16.
23. Jin Z, Cheng X, Feng H, et al. Apatinib inhibits angiogenesis via suppressing Akt/GSK3β/ANG signaling pathway in anaplastic thyroid cancer. Cell Physiol Biochem, 2017, 44(4): 1471-1484.
24. Liu RM, Sun DN, Jiao YL, et al. Macrophage migration inhibitory factor promotes tumor aggressiveness of esophageal squamous cell carcinoma via activation of Akt and inactivation of GSK3β. Cancer Lett, 2018, 412: 289-296.
25. Sokolosky M, Chappell WH, Stadelman K, et al. Inhibition of GSK-3β activity can result in drug and hormonal resistance and alter sensitivity to targeted therapy in MCF-7 breast cancer cells. Cell Cycle, 2014, 13(5): 820-833.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

ADAM17-shRNA promotes apoptosis of HT29 colon cancer cells through Akt/GSK3β signaling pathway

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