Liver Cancer
Copyright ©The Author(s) 2003. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 15, 2003; 9(2): 271-275
Published online Feb 15, 2003. doi: 10.3748/wjg.v9.i2.271
Study on the mechanism of epidermal growth factor-induced proliferation of hepatoma cells
Bin-Wen Wu, Yuan Wu, Jia-Long Wang, Ju-Sheng Lin, Shu-Yu Yuan, Ai Li, Wu-Ren Cui
Bin-Wen Wu, Jia-Long Wang, Ju-Sheng Lin, Shu-Yu Yuan, Ai Li, Institute of Liver Disease, Tongji Hospital, Tongji Medical College, HuaZhong Sci.and Tech. University, Wuhan, 430030, HuBei Province, China
Yuan Wu, Shenzheng hospital, Beijing University, Shenzheng, Guangdong Province, China
Wu-Ren Cui, Department of Nuclear Medicine, Tongji Medical College, HuaZhong Sci.and Tech. University, WuHan, 430030, HuBei Province, China
Author contributions: All authors contributed equally to the work.
Correspondence to: Jia-Long Wang, Institute of Liver Disease, Tongji Hospital, HuaZhong Sci.and Tech. University, 1095 JieFang AV., Wuhan, 430030, HuBei Province, China. whjlwang@163.net
Telephone: +86-27-83662578
Received: April 11, 2001
Revised: January 4, 2002
Accepted: March 18, 2002
Published online: February 15, 2003
Abstract

AIM: Many growth factors, such as epidermal growth factor (EGF), are associated with the carcinogenesis. EGF plays its role in the proliferation of hepatoma cells through binding with EGF receptor (EGFR) and a series of signal transduction. But the postreceptor pathway is still not clear. In the present experiment, we studied the effect of tyrosine kinase, protein kinase C, Na+/H+ exchange, calmodulin and voltage-dependent Ca2+ channel on EGF-induced hepatoma cell proliferation.

METHODS: Hepatoma cell line SMMC7721 was cultured in RPMI1640 serum-free medium. In order to study the effect of thyrosine kinase, protein kinase C, Na+/H+ exchange, calmodulin and voltage-dependent Ca2+ channel on human heptoma cell proliferation induced by epidermal growth factor (EGF), DNA synthesis rate of hepatoma cells was measured by the method of 3H-TdR incorporation.

RESULTS: EGF (10-9 M) stimulated the proliferation of heptoma cells significantly (3H-TdR incorporation was 1880 ± 281 cpm/well, P < 0.05), and this effect was significantly inhibited by tyrosine kinase inhibitor genistein (3H-TdR incorporation was 808 ± 209 cpm/well, P < 0.001). Calmodulin inhibitor W-7, protein kinase C inhibitor H-7 and Na+/H+ exchange inhibitor amiloride individually had significant inhibiting effect on EGF-induced proliferation of hepatoma cells (3H-TdR incorporation was 978 ± 87.3 cpm/well, 1241 ± 147 cpm/well, 1380 ± 189 cpm/well, respectivly, P < 0.001, P < 0.01, P < 0.05), but they all had no effect on the basal level proliferation of cultured hepatoma cells (3H-TdR incorporation was 1284 ± 260 cpm/well, 1179 ± 150 cpm/well, 1392 ± 152 cpm/well, respectivly, 3H-TdR incorporation of the control was 1353 ± 175 cpm/well, P > 0.05). Voltage-dependent Ca2+ channel inhibitor verapamil had no inhibition on EGF-induced proliferation of hepatoma cells (3H-TdR incorporation was 1637 ± 133 cpm/well, P > 0.05), it also had no effect on the basal level proliferation of cultured hepatoma cells (3H-TdR incorporation was 1196 ± 12 cpm/well, P > 0.05).

CONCLUSION: Our data suggest that tyrosine kinase, Ca2+-calmodulin-dependent pathway, protein kinase C and Na+/H+ exchange play a critical role in EGF-induced proliferation of hepatoma cells and that the effect of EGF is independent of voltage-dependent Ca2+ channel.

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