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Matrine derivative WM130 inhibits hepatocellular carcinoma by suppressing EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways.
Cancer Lett. 2015 Nov 01; 368(1):126-134.CL

Abstract

Matrine, a sophora alkaloid, has been demonstrated to exert antitumor effects on many types of cancer. However, its bioactivity is weak and its potential druggability is low. We modified the structure of matrine and obtained a new matrine derivative, WM130 (C30N4H40SO5F), which exhibited better pharmacological activities than matrine. In this study, we investigated the antitumor activity and the underlying mechanisms of WM130 on hepatocellular carcinoma (HCC) cells in vitro and in vivo, and found that WM130 inhibited the proliferation, invasion, migration and induced apoptosis of HCC cells in a dose-dependent manner. Furthermore, after treatment with WM130, the expressions of p-EGFR, p-ERK, p-AKT, MMP-2 and the ratio of Bcl-2/Bax were significantly down-regulated, whereas the expression of PTEN was increased in HCC cells. Moreover, WM130 inhibited Huh-7 xenograft tumor growth in a dose-dependent manner after intravenous administration. Immunohistochemistry results demonstrated that WM130 treatment resulted in down-regulation of p-EGFR, MMP-2, and Ki67 and up-regulation of PTEN. The findings indicated that WM130 could inhibit cell proliferation, invasion, migration and induced apoptosis in HCC cells by suppressing EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways and may be a novel effective candidate for HCC treatment.

Authors+Show Affiliations

Department of General Surgery, Wujiang No. 1 People's Hospital, Suzhou 215200, China; Department of Molecular Oncology, Eastern Hepatobiliary Surgery Hospital & National Center of Liver Cancer, Second Military Medical University, Shanghai 200438, China.Department of General Surgery, Wujiang No. 1 People's Hospital, Suzhou 215200, China.Department of Molecular Oncology, Eastern Hepatobiliary Surgery Hospital & National Center of Liver Cancer, Second Military Medical University, Shanghai 200438, China.Department of Molecular Oncology, Eastern Hepatobiliary Surgery Hospital & National Center of Liver Cancer, Second Military Medical University, Shanghai 200438, China.Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.Deparment of Cardiothoracic Surgery, No. 105 Hospital of PLA, Hefei 230031, China.Department of General Surgery, Wujiang No. 1 People's Hospital, Suzhou 215200, China. Electronic address: wjyygqg@sohu.com.Department of Molecular Oncology, Eastern Hepatobiliary Surgery Hospital & National Center of Liver Cancer, Second Military Medical University, Shanghai 200438, China. Electronic address: suchangqing@gmail.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26259512

Citation

Qian, Liqiang, et al. "Matrine Derivative WM130 Inhibits Hepatocellular Carcinoma By Suppressing EGFR/ERK/MMP-2 and PTEN/AKT Signaling Pathways." Cancer Letters, vol. 368, no. 1, 2015, pp. 126-134.
Qian L, Liu Y, Xu Y, et al. Matrine derivative WM130 inhibits hepatocellular carcinoma by suppressing EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways. Cancer Lett. 2015;368(1):126-134.
Qian, L., Liu, Y., Xu, Y., Ji, W., Wu, Q., Liu, Y., Gao, Q., & Su, C. (2015). Matrine derivative WM130 inhibits hepatocellular carcinoma by suppressing EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways. Cancer Letters, 368(1), 126-134. https://doi.org/10.1016/j.canlet.2015.07.035
Qian L, et al. Matrine Derivative WM130 Inhibits Hepatocellular Carcinoma By Suppressing EGFR/ERK/MMP-2 and PTEN/AKT Signaling Pathways. Cancer Lett. 2015 Nov 1;368(1):126-134. PubMed PMID: 26259512.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Matrine derivative WM130 inhibits hepatocellular carcinoma by suppressing EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways. AU - Qian,Liqiang, AU - Liu,Yan, AU - Xu,Yang, AU - Ji,Weidan, AU - Wu,Qiuye, AU - Liu,Yongjing, AU - Gao,Quangen, AU - Su,Changqing, Y1 - 2015/08/07/ PY - 2015/06/27/received PY - 2015/07/27/revised PY - 2015/07/31/accepted PY - 2015/8/12/entrez PY - 2015/8/12/pubmed PY - 2015/12/15/medline KW - Apoptosis KW - Hepatocellular carcinoma KW - Matrine derivative KW - Signaling KW - Therapeutic effect SP - 126 EP - 134 JF - Cancer letters JO - Cancer Lett VL - 368 IS - 1 N2 - Matrine, a sophora alkaloid, has been demonstrated to exert antitumor effects on many types of cancer. However, its bioactivity is weak and its potential druggability is low. We modified the structure of matrine and obtained a new matrine derivative, WM130 (C30N4H40SO5F), which exhibited better pharmacological activities than matrine. In this study, we investigated the antitumor activity and the underlying mechanisms of WM130 on hepatocellular carcinoma (HCC) cells in vitro and in vivo, and found that WM130 inhibited the proliferation, invasion, migration and induced apoptosis of HCC cells in a dose-dependent manner. Furthermore, after treatment with WM130, the expressions of p-EGFR, p-ERK, p-AKT, MMP-2 and the ratio of Bcl-2/Bax were significantly down-regulated, whereas the expression of PTEN was increased in HCC cells. Moreover, WM130 inhibited Huh-7 xenograft tumor growth in a dose-dependent manner after intravenous administration. Immunohistochemistry results demonstrated that WM130 treatment resulted in down-regulation of p-EGFR, MMP-2, and Ki67 and up-regulation of PTEN. The findings indicated that WM130 could inhibit cell proliferation, invasion, migration and induced apoptosis in HCC cells by suppressing EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways and may be a novel effective candidate for HCC treatment. SN - 1872-7980 UR - https://www.unboundmedicine.com/medline/citation/26259512/Matrine_derivative_WM130_inhibits_hepatocellular_carcinoma_by_suppressing_EGFR/ERK/MMP_2_and_PTEN/AKT_signaling_pathways_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3835(15)00501-7 DB - PRIME DP - Unbound Medicine ER -