Effect of p27KIP1 on cell cycle and apoptosis in gastric cancer cells

doi:10.3748/wjg.v11.i45.7072

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Dec 7, 2005 (publication date) through Jun 4, 2024

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Gastric Cancer

World J Gastroenterol. Dec 7, 2005; 11(45): 7072-7077
Published online Dec 7, 2005. doi: 10.3748/wjg.v11.i45.7072

Effect of p27^KIP1 on cell cycle and apoptosis in gastric cancer cells

Jian-Yong Zheng, Wei-Zhong Wang, Kai-Zong Li, Wen-Xian Guan, Wei Yan

Jian-Yong Zheng, Wei-Zhong Wang, Wen-Xian Guan, Department of Gastrointestinal Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China

Kai-Zong Li, Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China

Wei Yan, Department of Pathology, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China

Author contributions: All authors contributed equally to the work.

Correspondence to: Jian-Yong Zheng, Department of Gastrointestinal Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China. zhengjy2000@sohu.com

Telephone: +86-29-83375265

Received: November 16, 2004
Revised: May 23, 2005
Accepted: May 26, 2005
Published online: December 7, 2005

Abstract

AIM: To elucidate the effect of p27^KIP1 on cell cycle and apoptosis regulation in gastric carcinoma cells.

METHODS: The whole length of p27^KIP1 cDNA was transfected into human gastric cancer cell line SCG7901 by lipofectamine. Expression of p27^KIP1 protein or mRNA was analyzed by Western blot and RNA dot blotting, respectively. Effect of p27^KIP1 on cell growth was observed by MTT assay and anchorage-independent growth in soft agar. Tumorigenicity in nude mice was used to assess the in vivo biological effect of p27^KIP1. Flow cytometry, TUNEL, and electron microscopy were used to assess the effect of p27^KIP1 on cell cycle and apoptosis.

RESULTS: Expression of p27^KIP1 protein or mRNA increased evidently in SCG7901 cells transfected with p27^KIP1. The cell growth was reduced by 31% at 48 h after induction with zinc determined by cell viability assay. The alteration of cell malignant phenotype was evidently indicated by the loss of anchorage-independent growth ability in soft agar. The tumorigenicity in nude mice was reduced evidently (0.55±0.14 cm vs 1.36±0.13 cm, P<0.01). p27^KIP1 overexpression caused cell arrest with 36% increase (from 33.7% to 69.3%, P<0.01) in G₁ population. Prolonged p27^KIP1 expression induced apoptotic cell death reflected by pre-G1 peak in the histogram of FACS, which was also confirmed by TUNEL assay and electron microscopy.

CONCLUSION: p27^KIP1 can prolong cell cycle in G1 phase and lead to apoptosis. p27^KIP1 may be a good candidate for cancer gene therapy.

Keywords: Cell cycle, Apoptosis, Gastric neoplasm, p27^KIP1