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PNAS-4, a novel pro-apoptotic gene, can potentiate antineoplastic effects of cisplatin.
Cancer Chemother Pharmacol. 2009 Dec; 65(1):13-25.CC

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.

Authors+Show 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.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19387645

Citation

Yuan, Zhu, et al. "PNAS-4, a Novel Pro-apoptotic Gene, Can Potentiate Antineoplastic Effects of Cisplatin." Cancer Chemotherapy and Pharmacology, vol. 65, no. 1, 2009, pp. 13-25.
Yuan Z, Yan F, Wang YS, et al. PNAS-4, a novel pro-apoptotic gene, can potentiate antineoplastic effects of cisplatin. Cancer Chemother Pharmacol. 2009;65(1):13-25.
Yuan, Z., Yan, F., Wang, Y. S., Liu, H. Y., Gou, L. T., Zhao, X. Y., Lai, S. T., Deng, H. X., Li, J., Ding, Z. Y., Xiong, S. Q., Kan, B., Mao, Y. Q., Chen, L. J., Wei, Y. Q., & Zhao, X. (2009). PNAS-4, a novel pro-apoptotic gene, can potentiate antineoplastic effects of cisplatin. Cancer Chemotherapy and Pharmacology, 65(1), 13-25. https://doi.org/10.1007/s00280-009-0998-5
Yuan Z, et al. PNAS-4, a Novel Pro-apoptotic Gene, Can Potentiate Antineoplastic Effects of Cisplatin. Cancer Chemother Pharmacol. 2009;65(1):13-25. PubMed PMID: 19387645.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PNAS-4, a novel pro-apoptotic gene, can potentiate antineoplastic effects of cisplatin. AU - Yuan,Zhu, AU - Yan,Fei, AU - Wang,Yong-sheng, AU - Liu,Huan-yi, AU - Gou,Lan-tu, AU - Zhao,Xin-yu, AU - Lai,Song-tao, AU - Deng,Hong-xin, AU - Li,Jiong, AU - Ding,Zhen-yu, AU - Xiong,Shao-qun, AU - Kan,Bing, AU - Mao,Yong-qiu, AU - Chen,Li-juan, AU - Wei,Yu-quan, AU - Zhao,Xia, Y1 - 2009/04/22/ PY - 2008/12/02/received PY - 2009/04/03/accepted PY - 2009/4/24/entrez PY - 2009/4/24/pubmed PY - 2009/10/14/medline SP - 13 EP - 25 JF - Cancer chemotherapy and pharmacology JO - Cancer Chemother Pharmacol VL - 65 IS - 1 N2 - 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. SN - 1432-0843 UR - https://www.unboundmedicine.com/medline/citation/19387645/PNAS_4_a_novel_pro_apoptotic_gene_can_potentiate_antineoplastic_effects_of_cisplatin_ L2 - https://dx.doi.org/10.1007/s00280-009-0998-5 DB - PRIME DP - Unbound Medicine ER -