Enhanced antitumor effect of cisplatin in human NSCLC cells by tumor suppressor LKB1

W. Ou, S. Ye, W. Yang, Yidong Wang, Q. Ma, C. Yu, H. Shi, Z. Yuan, G. Zhong, J. Ren, W. Zhu, Y. Wei

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

LKB1 is a novel candidate tumor suppressor gene in lung cancer. In this study, we evaluated the effect of cationic liposomes (LPs)-mediated LKB1 gene (LPs-pVAX-LKB1) on low-dose cisplatin (cis-diamminedichloroplatinum)-mediated antitumor activity in lung cancer, both in vitro and in vivo. Our study demonstrated that cationic LPs-mediated LKB1 gene therapy could sensitize the response of lung cancer cells to cisplatin, and significantly induce apoptosis and inhibit proliferation, invasion and metastasis, compared with control groups. Combined treatment with intratumoral administration of Lps-pVAX-LKB1 and intraperitoneal injection of low-dose cisplatin into subcutaneous A549 lung tumor xenograft resulted in significant (P<0.01) inhibition of tumor growth. Furthermore, combined treatment with intravenous injections of Lps-pVAX-LKB1 and intraperitoneal injection of low-dose cisplatin into mice bearing experimental A549 lung metastasis demonstrated significant (P<0.01) decrease in the number of lung metastatic tumor nodules. Mice life spans of combination treatment group were also dramatically prolonged, compared with controls. Further studies indicated that LKB1-enhancing cisplatin-mediated antitumor effects might be associated with the upregulation of p-p53 and p-JNK, and downregulation of p-mammalian target of rapamycin, matrix metalloproteinase (MMP)-2 and MMP-9. This study suggests that the combination of LKB1 gene therapy with low-dose cisplatin-based chemotherapy may be a potent therapeutic strategy for lung cancer.

Original languageEnglish (US)
Pages (from-to)489-498
Number of pages10
JournalCancer Gene Therapy
Volume19
Issue number7
DOIs
StatePublished - Jul 2012
Externally publishedYes

Fingerprint

Cisplatin
Lung Neoplasms
Liposomes
Neoplasms
Intraperitoneal Injections
Genetic Therapy
Lung
Neoplasm Metastasis
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Sirolimus
Therapeutics
Tumor Suppressor Genes
Heterografts
Intravenous Injections
Up-Regulation
Down-Regulation
Apoptosis
Drug Therapy
Control Groups

Keywords

  • cisplatin
  • combination therapy
  • LKB1
  • lung cancer

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Molecular Biology

Cite this

Ou, W., Ye, S., Yang, W., Wang, Y., Ma, Q., Yu, C., ... Wei, Y. (2012). Enhanced antitumor effect of cisplatin in human NSCLC cells by tumor suppressor LKB1. Cancer Gene Therapy, 19(7), 489-498. https://doi.org/10.1038/cgt.2012.18

Enhanced antitumor effect of cisplatin in human NSCLC cells by tumor suppressor LKB1. / Ou, W.; Ye, S.; Yang, W.; Wang, Yidong; Ma, Q.; Yu, C.; Shi, H.; Yuan, Z.; Zhong, G.; Ren, J.; Zhu, W.; Wei, Y.

In: Cancer Gene Therapy, Vol. 19, No. 7, 07.2012, p. 489-498.

Research output: Contribution to journalArticle

Ou, W, Ye, S, Yang, W, Wang, Y, Ma, Q, Yu, C, Shi, H, Yuan, Z, Zhong, G, Ren, J, Zhu, W & Wei, Y 2012, 'Enhanced antitumor effect of cisplatin in human NSCLC cells by tumor suppressor LKB1', Cancer Gene Therapy, vol. 19, no. 7, pp. 489-498. https://doi.org/10.1038/cgt.2012.18
Ou, W. ; Ye, S. ; Yang, W. ; Wang, Yidong ; Ma, Q. ; Yu, C. ; Shi, H. ; Yuan, Z. ; Zhong, G. ; Ren, J. ; Zhu, W. ; Wei, Y. / Enhanced antitumor effect of cisplatin in human NSCLC cells by tumor suppressor LKB1. In: Cancer Gene Therapy. 2012 ; Vol. 19, No. 7. pp. 489-498.
@article{c5de5d35eefa4db087bacff0a24287f6,
title = "Enhanced antitumor effect of cisplatin in human NSCLC cells by tumor suppressor LKB1",
abstract = "LKB1 is a novel candidate tumor suppressor gene in lung cancer. In this study, we evaluated the effect of cationic liposomes (LPs)-mediated LKB1 gene (LPs-pVAX-LKB1) on low-dose cisplatin (cis-diamminedichloroplatinum)-mediated antitumor activity in lung cancer, both in vitro and in vivo. Our study demonstrated that cationic LPs-mediated LKB1 gene therapy could sensitize the response of lung cancer cells to cisplatin, and significantly induce apoptosis and inhibit proliferation, invasion and metastasis, compared with control groups. Combined treatment with intratumoral administration of Lps-pVAX-LKB1 and intraperitoneal injection of low-dose cisplatin into subcutaneous A549 lung tumor xenograft resulted in significant (P<0.01) inhibition of tumor growth. Furthermore, combined treatment with intravenous injections of Lps-pVAX-LKB1 and intraperitoneal injection of low-dose cisplatin into mice bearing experimental A549 lung metastasis demonstrated significant (P<0.01) decrease in the number of lung metastatic tumor nodules. Mice life spans of combination treatment group were also dramatically prolonged, compared with controls. Further studies indicated that LKB1-enhancing cisplatin-mediated antitumor effects might be associated with the upregulation of p-p53 and p-JNK, and downregulation of p-mammalian target of rapamycin, matrix metalloproteinase (MMP)-2 and MMP-9. This study suggests that the combination of LKB1 gene therapy with low-dose cisplatin-based chemotherapy may be a potent therapeutic strategy for lung cancer.",
keywords = "cisplatin, combination therapy, LKB1, lung cancer",
author = "W. Ou and S. Ye and W. Yang and Yidong Wang and Q. Ma and C. Yu and H. Shi and Z. Yuan and G. Zhong and J. Ren and W. Zhu and Y. Wei",
year = "2012",
month = "7",
doi = "10.1038/cgt.2012.18",
language = "English (US)",
volume = "19",
pages = "489--498",
journal = "Cancer Gene Therapy",
issn = "0929-1903",
publisher = "Nature Publishing Group",
number = "7",

}

TY - JOUR

T1 - Enhanced antitumor effect of cisplatin in human NSCLC cells by tumor suppressor LKB1

AU - Ou, W.

AU - Ye, S.

AU - Yang, W.

AU - Wang, Yidong

AU - Ma, Q.

AU - Yu, C.

AU - Shi, H.

AU - Yuan, Z.

AU - Zhong, G.

AU - Ren, J.

AU - Zhu, W.

AU - Wei, Y.

PY - 2012/7

Y1 - 2012/7

N2 - LKB1 is a novel candidate tumor suppressor gene in lung cancer. In this study, we evaluated the effect of cationic liposomes (LPs)-mediated LKB1 gene (LPs-pVAX-LKB1) on low-dose cisplatin (cis-diamminedichloroplatinum)-mediated antitumor activity in lung cancer, both in vitro and in vivo. Our study demonstrated that cationic LPs-mediated LKB1 gene therapy could sensitize the response of lung cancer cells to cisplatin, and significantly induce apoptosis and inhibit proliferation, invasion and metastasis, compared with control groups. Combined treatment with intratumoral administration of Lps-pVAX-LKB1 and intraperitoneal injection of low-dose cisplatin into subcutaneous A549 lung tumor xenograft resulted in significant (P<0.01) inhibition of tumor growth. Furthermore, combined treatment with intravenous injections of Lps-pVAX-LKB1 and intraperitoneal injection of low-dose cisplatin into mice bearing experimental A549 lung metastasis demonstrated significant (P<0.01) decrease in the number of lung metastatic tumor nodules. Mice life spans of combination treatment group were also dramatically prolonged, compared with controls. Further studies indicated that LKB1-enhancing cisplatin-mediated antitumor effects might be associated with the upregulation of p-p53 and p-JNK, and downregulation of p-mammalian target of rapamycin, matrix metalloproteinase (MMP)-2 and MMP-9. This study suggests that the combination of LKB1 gene therapy with low-dose cisplatin-based chemotherapy may be a potent therapeutic strategy for lung cancer.

AB - LKB1 is a novel candidate tumor suppressor gene in lung cancer. In this study, we evaluated the effect of cationic liposomes (LPs)-mediated LKB1 gene (LPs-pVAX-LKB1) on low-dose cisplatin (cis-diamminedichloroplatinum)-mediated antitumor activity in lung cancer, both in vitro and in vivo. Our study demonstrated that cationic LPs-mediated LKB1 gene therapy could sensitize the response of lung cancer cells to cisplatin, and significantly induce apoptosis and inhibit proliferation, invasion and metastasis, compared with control groups. Combined treatment with intratumoral administration of Lps-pVAX-LKB1 and intraperitoneal injection of low-dose cisplatin into subcutaneous A549 lung tumor xenograft resulted in significant (P<0.01) inhibition of tumor growth. Furthermore, combined treatment with intravenous injections of Lps-pVAX-LKB1 and intraperitoneal injection of low-dose cisplatin into mice bearing experimental A549 lung metastasis demonstrated significant (P<0.01) decrease in the number of lung metastatic tumor nodules. Mice life spans of combination treatment group were also dramatically prolonged, compared with controls. Further studies indicated that LKB1-enhancing cisplatin-mediated antitumor effects might be associated with the upregulation of p-p53 and p-JNK, and downregulation of p-mammalian target of rapamycin, matrix metalloproteinase (MMP)-2 and MMP-9. This study suggests that the combination of LKB1 gene therapy with low-dose cisplatin-based chemotherapy may be a potent therapeutic strategy for lung cancer.

KW - cisplatin

KW - combination therapy

KW - LKB1

KW - lung cancer

UR - http://www.scopus.com/inward/record.url?scp=84863721162&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863721162&partnerID=8YFLogxK

U2 - 10.1038/cgt.2012.18

DO - 10.1038/cgt.2012.18

M3 - Article

C2 - 22576699

AN - SCOPUS:84863721162

VL - 19

SP - 489

EP - 498

JO - Cancer Gene Therapy

JF - Cancer Gene Therapy

SN - 0929-1903

IS - 7

ER -