Bie Jia Jian Pill Combined with Bone Mesenchymal Stem Cells Regulates MicroRNA-140 to Suppress Hepatocellular Carcinoma Stem Cells

Overview

Journal Int J Stem Cells

Date 2021 Feb 26

PMID 33632990

Citations 2

Authors

Huang Jingjing

Huang Hongna

Zhang Wenfu

Lv Jianlin

Huang Guochu

Lin Yuanjia

Chen Songlin

Hu Yueqiang

Affiliations

Soon will be listed here.

Abstract

Background And Objectives: Cancer stem cells (CSCs) with tumorigenic potential are reported as the crucial factors of hepatocellular carcinoma (HCC) recurrence and therapy resistance. Bone mesenchymal stem cells (BMSCs) are documented to play an important role in the protection of hepatocytes. Bie Jia Jian pill (BJJP), a Traditional Chinese Medicine, has been used to treat liver fibrosis and liver cancer. This study aimed to explore the potential role of combined use of BJJP with BMSCs in HCC cell lines.

Methods And Results: Flow cytometry was used to identify BMSCs isolated from BALB/c mice and CSCs enriched from Huh7 cells by measuring CD24, CD133, CD44, CD73, CD105, CD166, CD29, CD14 and CD34. Differentiation potential of BMSCs was also determined. Cell viability and proliferation ability of CSCs were determined by CCK-8 assay and clone formation assay. The expressions of CSCs biomarkers and Wnt/-catenin signal pathway related proteins were determined by PCR and western blot. TOP-Flash/FOP-Flash luciferase assay was applied to measure the activity of -catenin/TCF. Compared with untreated CSCs, BJJP or BMSCs treatment alone on CSCs lead to increased miR-140 expression and cell apoptosis, as well as decreased expressions of CD24, CD133, EpCAM and cell viability. Downregualted expressions of Wnt/-catenin signal pathway related proteins, Wnt3a and -catenin were found in response to BJJP or BMSCs treatment alone. The combination of BJJP＋BMSCs treatment on CSCs could further enhance the suppressive effect on CSCs. Down-regulation of miR-140 in CSCs partially blocked the effects of BMSCs or BMSCs＋BJJP on the expressions of Wnt3a and -catenin as well as the cell viability and apoptosis of CSCs. Reversed expression pattern was found in CSCs transfected with miR-140 overexpression.

Conclusions: Taken together, we demonstrate that BJJP＋BMSCs together could further enhance the suppressive effect on CSCs through regulating miR-140 and suppressing Wnt/-catenin signal pathway. This study demonstrated the potential of BJJP＋BMSCs in therapeutic treatment of HCC.

Citing Articles

Ferulic Acid Combined With Bone Marrow Mesenchymal Stem Cells Attenuates the Activation of Hepatic Stellate Cells and Alleviates Liver Fibrosis.

Zhang R, Li W, Jiang X, Cui X, You H, Tang Z Front Pharmacol. 2022; 13:863797.

PMID: 35721175 PMC: 9205407. DOI: 10.3389/fphar.2022.863797.

Encouraging specific biomarkers-based therapeutic strategies for hepatocellular carcinoma.

Yao M, Yang J, Wang D, Wang L, Chen Y, Yao D World J Clin Cases. 2022; 10(11):3321-3333.

PMID: 35611205 PMC: 9048543. DOI: 10.12998/wjcc.v10.i11.3321.

References

Wu D, Zhang J, Lu Y, Bo S, Li L, Wang L . miR-140-5p inhibits the proliferation and enhances the efficacy of doxorubicin to breast cancer stem cells by targeting Wnt1. Cancer Gene Ther. 2018; 26(3-4):74-82. DOI: 10.1038/s41417-018-0035-0. View

Wang Z, Yang S, Huang J, Chen S, Li Q, Li Y . Effect of Rougan Huaqian granules combined with human mesenchymal stem cell transplantation on liver fibrosis in cirrhosis rats. Asian Pac J Trop Med. 2014; 7(7):576-81. DOI: 10.1016/S1995-7645(14)60097-3. View

Schwartz R, Reyes M, Koodie L, Jiang Y, Blackstad M, Lund T . Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. J Clin Invest. 2002; 109(10):1291-302. PMC: 150983. DOI: 10.1172/JCI15182. View

Serakinci N, Tulay P, Kalkan R . Role of Mesenchymal Stem Cells in Cancer Development and Their Use in Cancer Therapy. Adv Exp Med Biol. 2017; 1083:45-62. DOI: 10.1007/5584_2017_64. View

Acikgoz E, Tatar C, Oktem G . Triptolide inhibits CD133 /CD44 colon cancer stem cell growth and migration through triggering apoptosis and represses epithelial-mesenchymal transition via downregulating expressions of snail, slug, and twist. J Cell Biochem. 2020; 121(5-6):3313-3324. DOI: 10.1002/jcb.29602. View

Park D, Sung P, Kim J, Lee G, Jang J, Jung E . EpCAM-high liver cancer stem cells resist natural killer cell-mediated cytotoxicity by upregulating CEACAM1. J Immunother Cancer. 2020; 8(1). PMC: 7206970. DOI: 10.1136/jitc-2019-000301. View

Hou J, Zhao N, Zhu P, Chang J, Du Y, Shen W . Irradiated mesenchymal stem cells support stemness maintenance of hepatocellular carcinoma stem cells through Wnt/β-catenin signaling pathway. Cell Biosci. 2020; 10:93. PMC: 7398068. DOI: 10.1186/s13578-020-00449-5. View

Mahboudi H, Soleimani M, Hanaee-Ahvaz H, Ghanbarian H, Bandehpour M, Enderami S . New Approach for Differentiation of Bone Marrow Mesenchymal Stem Cells Toward Chondrocyte Cells With Overexpression of MicroRNA-140. ASAIO J. 2017; 64(5):662-672. DOI: 10.1097/MAT.0000000000000688. View

Hong I, Lee H, Kang K . Mesenchymal stem cells and cancer: friends or enemies?. Mutat Res. 2014; 768:98-106. DOI: 10.1016/j.mrfmmm.2014.01.006. View

10.

Zhao G, Yin Y, Zhao B . miR-140-5p is negatively correlated with proliferation, invasion, and tumorigenesis in malignant melanoma by targeting SOX4 via the Wnt/β-catenin and NF-κB cascades. J Cell Physiol. 2019; 235(3):2161-2170. DOI: 10.1002/jcp.29122. View

11.

Wu Y, Zhang J, Zhang X, Zhou H, Liu G, Li Q . Cancer Stem Cells: A Potential Breakthrough in HCC-Targeted Therapy. Front Pharmacol. 2020; 11:198. PMC: 7068598. DOI: 10.3389/fphar.2020.00198. View

12.

Liu X, Li M, Wang X, Dang Z, Yu L, Wang X . Effects of adjuvant traditional Chinese medicine therapy on long-term survival in patients with hepatocellular carcinoma. Phytomedicine. 2019; 62:152930. DOI: 10.1016/j.phymed.2019.152930. View

13.

Wu J, Jiang N, Lin J, Liu X . STYXL1 promotes malignant progression of hepatocellular carcinoma via downregulating CELF2 through the PI3K/Akt pathway. Eur Rev Med Pharmacol Sci. 2020; 24(6):2977-2985. DOI: 10.26355/eurrev_202003_20662. View

14.

Wang Z, Yang S, Huang J, Chen S, Li Q, Li Y . Effect of bone marrow mesenchymal stem cells on the Smad expression of hepatic fibrosis rats. Asian Pac J Trop Med. 2014; 7(4):321-4. DOI: 10.1016/S1995-7645(14)60048-1. View

15.

Ma W, Zhu D, Li J, Chen X, Xie W, Jiang X . Coating biomimetic nanoparticles with chimeric antigen receptor T cell-membrane provides high specificity for hepatocellular carcinoma photothermal therapy treatment. Theranostics. 2020; 10(3):1281-1295. PMC: 6956810. DOI: 10.7150/thno.40291. View

16.

Rada T, Santos T, Marques A, Correlo V, Frias A, Castro A . Osteogenic differentiation of two distinct subpopulations of human adipose-derived stem cells: an in vitro and in vivo study. J Tissue Eng Regen Med. 2011; 6(1):1-11. DOI: 10.1002/term.388. View

17.

Yagi H, Kitagawa Y . The role of mesenchymal stem cells in cancer development. Front Genet. 2013; 4:261. PMC: 3842093. DOI: 10.3389/fgene.2013.00261. View

18.

Lu Z, Yu Y, Ding X, Jin D, Wang G, Zhou Y . LncRNA FLJ33360 accelerates the metastasis in hepatocellular carcinoma by targeting miRNA-140/MMP9 axis. Am J Transl Res. 2020; 12(2):583-591. PMC: 7061837. View

19.

Yang S, Li X, Shen W, Hu H, Li C, Han G . MicroRNA-140 Represses Esophageal Cancer Progression via Targeting ZEB2 to Regulate Wnt/β-Catenin Pathway. J Surg Res. 2020; 257:267-277. DOI: 10.1016/j.jss.2020.07.074. View

20.

Khakoo A, Pati S, Anderson S, Reid W, Elshal M, Rovira I . Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi's sarcoma. J Exp Med. 2006; 203(5):1235-47. PMC: 2121206. DOI: 10.1084/jem.20051921. View