Effect of oncogene Yap1 silencing combined with tanshinone ⅡA on Huh-7 hepatoma cells

Yinghui HONG; Mingliang YE; Jie LUO; Chun WANG; Jialiang LIU; Chao REN; Siyu LAN; Qiu ZHAO; Ying CHANG

doi:10.3969/j.issn.1001-5256.2021.02.020

Volume 37 Issue 2

Mar. 2021

Turn off MathJax

Article Contents

Article Navigation > Journal of Clinical Hepatology > 2021 > 37(2): 348-353

PDF( 3256 KB)

Effect of oncogene Yap1 silencing combined with tanshinone ⅡA on Huh-7 hepatoma cells

DOI: 10.3969/j.issn.1001-5256.2021.02.020

Yinghui HONG^{1, 2, 3},
Mingliang YE^{1, 2, 3},
Jie LUO^{1, 2, 3},
Chun WANG^{1, 2, 3},
Jialiang LIU^{1, 2, 3},
Chao REN^{1, 2, 3},
Siyu LAN^{1, 2, 3},
Qiu ZHAO^{1, 2, 3},
Ying CHANG^{1, 2, 3
,
,}

1.
Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430071, Chin
2.
Hubei Clinical Center of Intestinal and Colorectal Diseases, Wuhan 430071, China
3.
Hubei Key Laboratory of Intestinal and Colorectal Diseases, Wuhan 430071, China

Received Date: 2020-08-10
Accepted Date: 2020-09-04
Published Date: 2021-02-20

Abstract

Abstract

Objective To investigate the effect of the Yap1 gene and tanshinone ⅡA on the proliferation, migration, and invasion abilities of Huh-7 hepatoma cells. Methods A total of 10 pairs of human hepatocellular carcinoma (HCC) samples and adjacent tissue samples were collected in Zhongnan Hospital of Wuhan University from June 1 to December 1, 2019. Quantitative real-time PCR and Western blotting were used to measure the expression of the Yap1 gene and phenotype-related molecules. MTT cell proliferation detection reagent was used to measure the inhibition rate of cell proliferation after the treatment with different concentrations of tanshinone ⅡA. Western blotting was used to measure the changes in the expression of apoptosis-and migration-related markers after different interventions. Flow cytometry and Transwell assay were used to measure apoptosis and cell migration and invasion abilities. The data of 375 cases of liver cancer and 50 cases of relatively normal liver tissue samples were downloaded from The Cancer Genome Atlas, including clinicopathological information. The t-test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. Results In 8 of the 10 pairs of HCC samples and adjacent tissue samples, HCC samples had significantly higher expression of Yap1 than the adjacent tissue samples. Compared with the normal human liver epithelial cells L02, the Huh-7 and HCCL-M3 hepatoma cells had a significant increase in the expression of Yap1. The silencing efficiency of si-Yap1-3 transfection reached 87.004% at the protein level. MTT results showed that tanshinone ⅡA effectively inhibited the proliferation of Huh-7 cells, with a half inhibitory concentration of 8.683 μmol/L. After the cells were treated with si-Yap1-3 and tanshinone ⅡA, there was an increase in the expression of the downstream marker for proliferation and migration E-cadherin and a reduction in the expression of vimentin, and the results of Transwell assay showed that compared with the si-NC group, the tanshinone ⅡA+si-Yap1-3 group had significant reductions in the migration and invasion abilities of Huh-7 cells (migration: 43.19±2.88 vs 132.20±10.03, t=8.527, P=0.001; invasion: 53.95±4.20 vs 179.10±11.11, t=4.484, P=0.011). The group treated with si-Yap1-3 and tanshinone ⅡA had an increase in the expression of the apoptosis-related marker Bax and a reduction in the expression of Bcl-2, as well as a significantly higher early apoptosis rate than the si-NC group (25.98% vs 9.21%, χ²=4.078, P < 0.05). Conclusion Oncogene Yap1 silencing combined with tanshinone ⅡA can promote the apoptosis of Huh-7 hepatoma cells and inhibit their migration and invasion, which can provide certain guiding significance for clinical medication.
- Carcinoma, Hepatocellular,
- Gene Silencing,
- TANSHINONE

FullText(HTML)

References(13)

References

[1]	RAWLA P, SUNKARA T, MURALIDHARAN P, et al. Update in global trends and aetiology of hepatocellular carcinoma[J]. Contemp Oncol (Pozn), 2018, 22(3): 141-150.
[2]	XIAO Y, ZHANG H, MA Q, et al. YAP1-mediated pancreatic stellate cell activation inhibits pancreatic cancer cell proliferation[J]. Cancer Lett, 2019, 462: 51-60. DOI: 10.1016/j.canlet.2019.07.015
[3]	LU T, LI Z, YANG Y, et al. The Hippo/YAP1 pathway interacts with FGFR1 signaling to maintain stemness in lung cancer[J]. Cancer Lett, 2018, 423: 36-46. DOI: 10.1016/j.canlet.2018.02.015
[4]	GUO L, CHEN Y, LUO J, et al. YAP1 overexpression is associated with poor prognosis of breast cancer patients and induces breast cancer cell growth by inhibiting PTEN[J]. FEBS Open Bio, 2019, 9(3): 437-445. DOI: 10.1002/2211-5463.12597
[5]	HU Y, WANG S, WU X, et al. Chinese herbal medicine-derived compounds for cancer therapy: A focus on hepatocellular carcinoma[J]. J Ethnopharmacol, 2013, 149(3): 601-612. DOI: 10.1016/j.jep.2013.07.030
[6]	LIU B, LIU L, ZANG A, et al. Tanshinone ⅡA inhibits proliferation and induces apoptosis of human nasopharyngeal carcinoma cells via p53-cyclin B1/CDC2[J]. Oncol Lett, 2019, 18(3): 3317-3322.
[7]	GUO Y, LI Y, XIANG B, et al. Nutlin-3 plus tanshinone ⅡA exhibits synergetic anti-leukemia effect with imatinib by reactivating p53 and inhibiting the AKT/mTOR pathway in Ph+ ALL[J]. Biochem J, 2017, 474(24): 4153-4170. DOI: 10.1042/BCJ20170386
[8]	XUE J, JIN X, WAN X, et al. Effects and mechanism of tanshinone Ⅱ A in proliferation, apoptosis, and migration of human colon cancer cells[J]. Med Sci Monit, 2019, 25: 4793-4800. DOI: 10.12659/MSM.914446
[9]	FAIVRE S, RIMASSA L, FINN RS. Molecular therapies for HCC: Looking outside the box[J]. J Hepatol, 2020, 72(2): 342-352. DOI: 10.1016/j.jhep.2019.09.010
[10]	KUDO M, FINN RS, QIN S, et al. Lenvatinib versus sorafenib B in first-line treatment of patients with unresectable hepatocellular carcinoma: A randomised phase 3 non-inferiority trial[J]. Lancet, 2018, 391(10126): 1163-1173. DOI: 10.1016/S0140-6736(18)30207-1
[11]	CHO ES, KANG HE, KIM NH, et al. Therapeutic implications of cancer epithelial-mesenchymal transition (EMT)[J]. Arch Pharm Res, 2019, 42(1): 14-24. DOI: 10.1007/s12272-018-01108-7
[12]	CHEN X, LI Y, LUO J, et al. Molecular mechanism of Hippo-YAP1/TAZ pathway in heart development, disease, and regeneration[J]. Front Physiol, 2020, 11: 389. DOI: 10.3389/fphys.2020.00389
[13]	EGE N, DOWBAJ AM, JIANG M, et al. Quantitative analysis reveals that actin and Src-family kinases regulate nuclear YAP1 and its export[J]. Cell Syst, 2018, 6(6): 692-708. DOI: 10.1016/j.cels.2018.05.006

Relative Articles

Supplements(0)

Cited By

Proportional views

Proportional views

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Figures(10) / Tables(2)

Get Citation

PDF

XML

Article Metrics

Article views (478) PDF downloads(20)

Effect of oncogene Yap1 silencing combined with tanshinone ⅡA on Huh-7 hepatoma cells

DOI: 10.3969/j.issn.1001-5256.2021.02.020

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

Effect of oncogene Yap1 silencing combined with tanshinone ⅡA on Huh-7 hepatoma cells

DOI: 10.3969/j.issn.1001-5256.2021.02.020

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

About Journal

Submission Guideline

Journal Online

Hepatobiliary College

Guidelines

Export File

Citation

Format

Content