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01-12-2009 | Original Article

PNAS-4, a novel pro-apoptotic gene, can potentiate antineoplastic effects of cisplatin

Authors: Zhu Yuan, Fei Yan, Yong-sheng Wang, Huan-yi Liu, Lan-tu Gou, Xin-yu Zhao, Song-tao Lai, Hong-xin Deng, Jiong Li, Zhen-yu Ding, Shao-qun Xiong, Bing Kan, Yong-qiu Mao, Li-juan Chen, Yu-quan Wei, Xia Zhao

Published in: Cancer Chemotherapy and Pharmacology | Issue 1/2009

Abstract

Purpose

PNAS-4, a novel pro-apoptotic gene activated during the early response to DNA damage, can inhibit proliferation via apoptosis when overexpressed in some tumor cells. The objectives of this study were to determine whether PNAS-4 could enhance apoptosis induced by cisplatin besides its induction of apoptosis, and to evaluate the usefulness of combined treatment with mouse PNAS-4 (mPNAS-4) gene therapy and low-dose cisplatin chemotherapy in the inhibition of tumor growth in colon carcinoma (CT26) and Lewis lung carcinoma (LL/2) murine models.

Methods

In this study, the in vitro growth-inhibitory and pro-apoptotic effects of PNAS-4 and/or cisplatin on CT26, LL/2, and SKOV3 cancer cells were assessed by MTT assay, flow cytometric analysis, DNA fragmentation, and morphological analysis, respectively. The in vivo antitumor activity of combined treatment with mPNAS-4 gene therapy and low-dose cisplatin were evaluated in the inhibition of tumor growth in colon carcinoma (CT26) and Lewis lung carcinoma (LL/2) murine models. Tumor volume and survival time were observed. Induction of apoptosis was also assessed in tumor tissues.

Results

In vitro, PNAS-4 inhibited proliferation of colon carcinoma (CT26), Lewis lung carcinoma (LL/2) and human ovarian cancer (SKOV3) cell lines via apoptosis, and significantly enhanced the apoptosis of CT26, LL/2, and SKOV3 cells induced by cisplatin. In vivo systemic administration of expression plasmid encoding mPNAS-4 (pcDNA3.1-mPS) and cisplatin, significantly decreased tumor growth through increased tumor cell apoptosis compared to treatment with mPNAS-4 or cisplatin alone.

Conclusions

Our data suggests that the combined treatment with mPNAS-4 plus cisplatin may augment the induction of apoptosis in tumor cells in vitro and in vivo, and that the augmented antitumor activity in vivo may result from the increased induction of apoptosis. The present study may provide a novel way to augment the antitumor efficacy of cytotoxic chemotherapy.

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Title: PNAS-4, a novel pro-apoptotic gene, can potentiate antineoplastic effects of cisplatin
Authors: Zhu Yuan
Fei Yan
Yong-sheng Wang
Huan-yi Liu
Lan-tu Gou
Xin-yu Zhao
Song-tao Lai
Hong-xin Deng
Jiong Li
Zhen-yu Ding
Shao-qun Xiong
Bing Kan
Yong-qiu Mao
Li-juan Chen
Yu-quan Wei
Xia Zhao
Publication date: 01-12-2009
Publisher: Springer-Verlag
Published in: Cancer Chemotherapy and Pharmacology / Issue 1/2009
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-009-0998-5

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Purpose

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