PNAS-4, a novel pro-apoptotic gene, can potentiate antineoplastic effects of cisplatin
Authors: Lan-tu Gou
Song-tao Lai
Yong-qiu Mao
Fei Yan
Huan-yi Liu
Xia Zhao
Li-juan Chen
Zhen-yu Ding
Bing Kan
Hong-xin Deng
Shao-qun Xiong
Yong-sheng Wang
Xin-yu Zhao
Jiong Li
Yu-quan Wei
Zhu Yuan
Journal: Cancer Chemotherapy and Pharmacology (2009)
Discipline: CLINICAL MEDICINE
Keywords: PNAS-4; apoptosis; cisplatin; gene therapy; tumor growth
Affiliations: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, 1# Keyuan Road 4, Gaopeng Street, High Technological Development Zone 610041, Chengdu, China.

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. 

Retracted: No

PubPeer comments:
null, 
 The partial overlaps extend to frame A. ![file] The crucial point is not so much that panels overlap, but that some cells are present in one overlap but not another. , 
 #2 Panel E is essentially the same as the others, but with additional cells. ![file] As Peer 1 noted at #1, panels B and C overlap apart from a rotation and the insertion of additional cells. ![file] All five illustrations of treatments appear to be modified enlargements of a singe image. , 
 hoyauff0cmind your own businessuff0cif you really have gutuff0cyou dont need to be anonymous just like a coward , 
 #4 Keep it civil please. There i no need for threatening language. Questions have been posed civility and they simply require answers. Your peers merely request an explanation for what is either a montage, which is not explained in the figure legends, or extraordinarily reproducible cell culture. The alternative is that the paper loses credibility with the community and future papers are viewed with suspicion. , 
 I have just posted a 2019 paper with possible image issues authored by several of these co-authors (including self-identified co-author #4) here: https: pubpeer.com publications 88A943478EF78002CC7D65D0E884F4#1 , 
  Mind my own business ? So the contents of a paper are not the business of people who read it? , 
 Dear Dr. Wang, dear other authors, I was Peer 1, and I reported this paper, together with 28 other papers to the journal in June 2015. I thank Hoya for their additional findings. It has been more than five years, and I would love to hear an explanation for what has happened to cause these panels to look some similar, and what has happened by the authors to address the problem. ,