Effects of Mifepristone on Proliferation of Human Gastric Adenocarcinoma Cell Line SGC-7901 in Vitro

Overview

Journal World J Gastroenterol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2004 Aug 17

PMID 15309708

Citations 10

Authors

Da-Qiang Li

Zhi-Biao Wang

Jin Bai

Jie Zhao

Yuan Wang

Kai Hu

Yong-Hong Du

Affiliations

Soon will be listed here.

Abstract

Aim: To explore the effects of mifepristone, a progesterone receptor (PR) antagonist, on the proliferation of human gastric adenocarcinoma cell line SGC-7 901 in vitro and the possible mechanisms involved.

Methods: In situ hybridization was used to detect the expression of PR mRNA in SGC-7901 cells. After treatment with various concentrations of mifepristone (2.5, 5, 10, 20 micromol/L) at various time intervals, the ultrastructural changes, cell proliferation, cell-cycle phase distribution, and the expression of caspase-3 and Bcl-XL were analyzed using transmission electron microscopy (TEM), tetrazolium blue(MTT) assay, 3H-TdR incorporation, flow cytometry, and reverse transcription-polymerase chain reaction (RT-PCR).

Results: Mifepristone markedly induced apoptosis and inhibited cell proliferation of PR- positive SGC-7901 cells revealed by TEM, MTT assay and 3H-TdR incorporation, in a dose- and time-dependent manner. The inhibitory rate was increased from 8.98% to 51.29%. Flow cytometric analysis showed mifepristone dose-dependently decreased cells in S and G2/M phases, increased cells in G0/G1 phase, reduced the proliferative index from 57.75% to 22.83%. In addition, mifepristone up-regulated the expression of caspase-3, and down- regulated the Bcl-XL expression, dose-dependently.

Conclusion: Mifepristone effectively inhibited the proliferation of PR-positive human gastric adenocarcinoma cell line SGC-7901 in vitro through multiple mechanisms, and may be a beneficial agent against human adenocarcinoma.

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References

El Etreby M, Liang Y, Wrenn R, Schoenlein P . Additive effect of mifepristone and tamoxifen on apoptotic pathways in MCF-7 human breast cancer cells. Breast Cancer Res Treat. 1999; 51(2):149-68. DOI: 10.1023/a:1006078032287. View

Valentini V, Cellini F, DAngelillo R . Combined treatments in gastric cancer: radiotherapy. Suppl Tumori. 2003; 2(5):S39-44. View

El Etreby M, Liang Y, Johnson M, Lewis R . Antitumor activity of mifepristone in the human LNCaP, LNCaP-C4, and LNCaP-C4-2 prostate cancer models in nude mice. Prostate. 2000; 42(2):99-106. DOI: 10.1002/(sici)1097-0045(20000201)42:2<99::aid-pros3>3.0.co;2-i. View

El Etreby M, Liang Y . Effect of antiprogestins and tamoxifen on growth inhibition of MCF-7 human breast cancer cells in nude mice. Breast Cancer Res Treat. 1998; 49(2):109-17. DOI: 10.1023/a:1006098910000. View

Thomas M, Monet J . Combined effects of RU486 and tamoxifen on the growth and cell cycle phases of the MCF-7 cell line. J Clin Endocrinol Metab. 1992; 75(3):865-70. DOI: 10.1210/jcem.75.3.1517379. View

Yokoyama Y, Shinohara A, Takahashi Y, Wan X, Takahashi S, Niwa K . Synergistic effects of danazol and mifepristone on the cytotoxicity of UCN-01 in hormone-responsive breast cancer cells. Anticancer Res. 2000; 20(5A):3131-5. View

Rocereto T, Saul H, Aikins Jr J, Paulson J . Phase II study of mifepristone (RU486) in refractory ovarian cancer. Gynecol Oncol. 2000; 77(3):429-32. DOI: 10.1006/gyno.2000.5789. View

Meyer M, Pornon A, Ji J, Bocquel M, Chambon P, Gronemeyer H . Agonistic and antagonistic activities of RU486 on the functions of the human progesterone receptor. EMBO J. 1990; 9(12):3923-32. PMC: 552163. DOI: 10.1002/j.1460-2075.1990.tb07613.x. View

De Paoli A, Buonadonna A, Boz G, Lombardi D, Innocente R, Tumolo S . Combined modality treatment for locally advanced gastric cancer. Suppl Tumori. 2003; 2(5):S58-62. View

10.

Schneider C, Gibb R, Taylor D, Wan T, Gercel-Taylor C . Inhibition of endometrial cancer cell lines by mifepristone (RU 486). J Soc Gynecol Investig. 1998; 5(6):334-8. DOI: 10.1016/s1071-5576(98)00037-9. View

11.

Korenaga D, Orita H, Okuyama T, Kinoshita J, Maekawa S, Ikeda T . Sex hormone-receptor-negative tumors have a higher proliferative activity than sex hormone-receptor-positive tumors in human adenocarcinomas of the gastrointestinal tract. Surg Today. 1998; 28(10):1007-14. DOI: 10.1007/BF02483953. View

12.

Lin V, Aw S, Ng E, Tan M . Demonstration of mixed properties of RU486 in progesterone receptor (PR)-transfected MDA-MB-231 cells: a model for studying the functions of progesterone analogues. Br J Cancer. 2001; 85(12):1978-86. PMC: 2364017. DOI: 10.1054/bjoc.2001.2167. View

13.

Matsui M, KOJIMA O, Kawakami S, Uehara Y, Takahashi T . The prognosis of patients with gastric cancer possessing sex hormone receptors. Surg Today. 1992; 22(5):421-5. DOI: 10.1007/BF00308791. View

14.

Macdonald J . Chemotherapy in the management of gastric cancer. J Clin Oncol. 2003; 21(23 Suppl):276s-279s. DOI: 10.1200/JCO.2003.09.137. View

15.

Maehara Y, Kakeji Y, Masuda T, Sakoguchi T, Imamura M, Ohgaki K . [Treatment of gastric cancer: current state and future prospect]. Fukuoka Igaku Zasshi. 2003; 94(10):285-95. View

16.

Yang X, Stennicke H, Wang B, Green D, Janicke R, Srinivasan A . Granzyme B mimics apical caspases. Description of a unified pathway for trans-activation of executioner caspase-3 and -7. J Biol Chem. 1998; 273(51):34278-83. DOI: 10.1074/jbc.273.51.34278. View

17.

Rose F, Barnea E . Response of human ovarian carcinoma cell lines to antiprogestin mifepristone. Oncogene. 1996; 12(5):999-1003. View

18.

Sridhar S, Ali A, Liang Y, El Etreby M, Lewis R, Kumar M . Differential expression of members of the tumor necrosis factor alpha-related apoptosis-inducing ligand pathway in prostate cancer cells. Cancer Res. 2001; 61(19):7179-83. View

19.

Lu J, Sun X, Dai D, Zhu S, Chang Q, Liu S . Epidemiology of gastroenterologic cancer in Henan Province, China. World J Gastroenterol. 2003; 9(11):2400-3. PMC: 4656509. DOI: 10.3748/wjg.v9.i11.2400. View

20.

Oshima C, Wonraht D, Catarino R, Mattos D, Forones N . Estrogen and progesterone receptors in gastric and colorectal cancer. Hepatogastroenterology. 2000; 46(30):3155-8. View