Qilan Preparation Inhibits Proliferation and Induces Apoptosis by Down-regulating MicroRNA-21 in Human Tca8113 Tongue Squamous Cell Carcinoma Cells

Overview

Journal J Tradit Chin Med

Date 2022 Sep 9

PMID 36083475

Authors

Ding Jiamin

Xing Yifeng

Chen Zuoliang

Chen Wanlu

M A Zhongxiong

Xie Yunde

Zhou Lin

Affiliations

Soon will be listed here.

Abstract

Objective: The aim of this study was to examine the antitumor effects of Qilan preparation on oral squamous cell carcinoma (OSCC) and to investigate its underlying mechanisms of action.

Methods: Cell proliferation, cell cycle distribution and apoptosis were examined using cell counting kit-8 (CCK8) and flow cytometry (FCM). The expression of PTEN and PDCD4 were determined by western blot. Changes in miR-21 levels were quantified using TaqMan stem-loop real-time PCR. After miR-21 was transiently transfected into Tca8113 cells using Lipofectamine®3000, cell proliferation, apoptosis and miR-21 and PDCD4 expression levels were measured.

Results: Qilan preparation inhibited Tca8113 cell growth in a dose- and time-dependent manner by inducing apoptosis and cell cycle arrest in S-phase, decreasing miR-21 levels and increasing PTEN and PDCD4 expression. MiR-21 overexpression reversed the Qilan preparation-induced suppression of cell proliferation and induction of apoptosis while also blocking the increase in PDCD4.

Conclusions: Our study revealed, for the first time, the ability of Qilan preparation to suppress TSCC cell growth and elucidated that Qilan preparation elicits its anti-cancer actions either the miR-21/PDCD4 or PTEN pathway.

References

Zhou X, Ren Y, Liu A, Han L, Zhang K, Li S . STAT3 inhibitor WP1066 attenuates miRNA-21 to suppress human oral squamous cell carcinoma growth in vitro and in vivo. Oncol Rep. 2014; 31(5):2173-80. DOI: 10.3892/or.2014.3114. View

Jansen A, Camalier C, Stark C, Colburn N . Characterization of programmed cell death 4 in multiple human cancers reveals a novel enhancer of drug sensitivity. Mol Cancer Ther. 2004; 3(2):103-10. View

Chen J, Lu K, Tsai M, Hsu S, Kuo C, Yang J . Gypenosides induced G0/G1 arrest via CHk2 and apoptosis through endoplasmic reticulum stress and mitochondria-dependent pathways in human tongue cancer SCC-4 cells. Oral Oncol. 2008; 45(3):273-83. DOI: 10.1016/j.oraloncology.2008.05.012. View

Hou J, Liu S, Ma Z, Lang X, Wang J, Liang Z . Effects of gynostemma pentaphyllum makino on the immunological function of cancer patients. J Tradit Chin Med. 1991; 11(1):47-52. View

Wei Z, Zhang X, Wang X, Gao F, Zhou C, Zhu F . PDCD4 inhibits the malignant phenotype of ovarian cancer cells. Cancer Sci. 2009; 100(8):1408-13. PMC: 11159598. DOI: 10.1111/j.1349-7006.2009.01210.x. View

Chen J, Wu A, Bamodu O, Yadav V, Chao T, Tzeng Y . Ovatodiolide Suppresses Oral Cancer Malignancy by Down-Regulating Exosomal Mir-21/STAT3/β-Catenin Cargo and Preventing Oncogenic Transformation of Normal Gingival Fibroblasts. Cancers (Basel). 2019; 12(1). PMC: 7017298. DOI: 10.3390/cancers12010056. View

Lankat-Buttgereit B, Lenschen B, Schmidt H, Goke R . The action of Pdcd4 may be cell type specific: evidence that reduction of dUTPase levels might contribute to its tumor suppressor activity in Bon-1 cells. Apoptosis. 2007; 13(1):157-64. DOI: 10.1007/s10495-007-0153-x. View

Brito J, Gomes C, Guimaraes A, Campos K, Gomez R . Relationship between microRNA expression levels and histopathological features of dysplasia in oral leukoplakia. J Oral Pathol Med. 2013; 43(3):211-6. DOI: 10.1111/jop.12112. View

Mo Q, Zhou G, Xie B, Ma B, Zang X, Chen Y . Evaluation of the hepatoprotective effect of Yigan mingmu oral liquid against acute alcohol-induced liver injury in rats. BMC Complement Med Ther. 2020; 20(1):32. PMC: 7076881. DOI: 10.1186/s12906-020-2817-9. View

10.

Lim L, Lau N, Garrett-Engele P, Grimson A, Schelter J, Castle J . Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 2005; 433(7027):769-73. DOI: 10.1038/nature03315. View

11.

Sansal I, Sellers W . The biology and clinical relevance of the PTEN tumor suppressor pathway. J Clin Oncol. 2004; 22(14):2954-63. DOI: 10.1200/JCO.2004.02.141. View

12.

Wang J, Li Y, Wang X, Jiang C . Ursolic acid inhibits proliferation and induces apoptosis in human glioblastoma cell lines U251 by suppressing TGF-β1/miR-21/PDCD4 pathway. Basic Clin Pharmacol Toxicol. 2012; 111(2):106-12. DOI: 10.1111/j.1742-7843.2012.00870.x. View

13.

Mestdagh P, Van Vlierberghe P, De Weer A, Muth D, Westermann F, Speleman F . A novel and universal method for microRNA RT-qPCR data normalization. Genome Biol. 2009; 10(6):R64. PMC: 2718498. DOI: 10.1186/gb-2009-10-6-r64. View

14.

Parsons R . Human cancer, PTEN and the PI-3 kinase pathway. Semin Cell Dev Biol. 2004; 15(2):171-6. DOI: 10.1016/j.semcdb.2003.12.021. View

15.

Li J, Huang H, Sun L, Yang M, Pan C, Chen W . MiR-21 indicates poor prognosis in tongue squamous cell carcinomas as an apoptosis inhibitor. Clin Cancer Res. 2009; 15(12):3998-4008. DOI: 10.1158/1078-0432.CCR-08-3053. View

16.

Ma W, Hu S, Xu Y, Li H, Ma X, Wei B . Haimufang decoction, a Chinese medicine formula for lung cancer, arrests cell cycle, stimulates apoptosis in NCI-H1975 cells, and induces M1 polarization in RAW 264.7 macrophage cells. BMC Complement Med Ther. 2020; 20(1):243. PMC: 7404932. DOI: 10.1186/s12906-020-03031-1. View

17.

Hu H, Li K, Wang X, Liu Y, Lu Z, Dong R . Set9, NF-κB, and microRNA-21 mediate berberine-induced apoptosis of human multiple myeloma cells. Acta Pharmacol Sin. 2012; 34(1):157-66. PMC: 4086496. DOI: 10.1038/aps.2012.161. View

18.

Yang H, Matthews C, Clair T, Wang Q, Baker A, Li C . Tumorigenesis suppressor Pdcd4 down-regulates mitogen-activated protein kinase kinase kinase kinase 1 expression to suppress colon carcinoma cell invasion. Mol Cell Biol. 2006; 26(4):1297-306. PMC: 1367180. DOI: 10.1128/MCB.26.4.1297-1306.2006. View

19.

Ren W, Wang X, Gao L, Li S, Yan X, Zhang J . MiR-21 modulates chemosensitivity of tongue squamous cell carcinoma cells to cisplatin by targeting PDCD4. Mol Cell Biochem. 2014; 390(1-2):253-62. DOI: 10.1007/s11010-014-1976-8. View

20.

Li L, Li X, Wang L, Du W, Guo R, Liang H . Matrine inhibits breast cancer growth via miR-21/PTEN/Akt pathway in MCF-7 cells. Cell Physiol Biochem. 2012; 30(3):631-41. DOI: 10.1159/000341444. View