This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nishizaki, M. Articles by Ji, L. Search for Related Content PubMed PubMed Citation Articles by Nishizaki, M. Articles by Ji, L.

Synergistic Inhibition of Human Lung Cancer Cell Growth by Adenovirus-mediated Wild-Type p53 Gene Transfer in Combination with Docetaxel and Radiation Therapeutics in Vitro and in Vivo¹

Division of Surgery, Department of Thoracic and Cardiovascular Surgery [M. N., J. A. R., L. J.], and Departments of Experimental Radiation Oncology [R. E. M.] and Biomathematics [L. B. L., E. N. A., R. A. W.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

Chemotherapy given sequentially or concurrently with external beam radiation therapy has emerged as a standard for the treatment of locally advanced lung cancer. Gene therapy by adenovirus-mediated wild-type p53 gene transfer has been shown to inhibit lung cancer growth in vitro, in animal models, and in human clinical trials. However, no information is available on the combined effects of p53 gene transfer, chemotherapy, and radiation therapy on lung cancer growth in vitro and in vivo. Therefore, we developed two-dimensional and three-dimensional isobologram modeling and statistical methods to evaluate the synergistic, additive, or antagonistic efficacy among these therapeutic agents in human non-small cell lung cancer cell lines A549, H460, H322, and H1299, at the ID₅₀ and ID₈₀ levels. The combination of these three therapeutic agents exhibited synergistic inhibitory effects on tumor cell growth in all four cell lines at both the ID₅₀ and the ID₈₀ levels in vitro. In mouse models with H1299 and A549 xenografts, combined treatment synergistically inhibited tumor growth in the absence of any apparent increase in toxicity, when compared with other treatment and control groups. Together, our findings suggest that a combination of gene therapy, chemotherapy, and radiation therapy may be an effective strategy for human cancer treatment.

This article has been cited by other articles:

				G. Jayachandran, J.-i. Sazaki, M. Nishizaki, K. Xu, L. Girard, J. D. Minna, J. A. Roth, and L. Ji Fragile Histidine Triad Mediated Tumor Suppression of Lung Cancer by Targeting Multiple Components of the Ras/Rho GTPase Molecular Switch Cancer Res., November 1, 2007; 67(21): 10379 - 10388. [Abstract] [Full Text] [PDF]

				S. Ohtani, A. Iwamaru, W. Deng, K. Ueda, G. Wu, G. Jayachandran, S. Kondo, E. N. Atkinson, J. D. Minna, J. A. Roth, et al. Tumor Suppressor 101F6 and Ascorbate Synergistically and Selectively Inhibit Non-Small Cell Lung Cancer Growth by Caspase-Independent Apoptosis and Autophagy Cancer Res., July 1, 2007; 67(13): 6293 - 6303. [Abstract] [Full Text] [PDF]

				S. Mazumder, D. Plesca, M. Kinter, and A. Almasan Interaction of a Cyclin E Fragment with Ku70 Regulates Bax-Mediated Apoptosis Mol. Cell. Biol., May 1, 2007; 27(9): 3511 - 3520. [Abstract] [Full Text] [PDF]

				W.-G. Deng, H. Kawashima, G. Wu, G. Jayachandran, K. Xu, J. D. Minna, J. A. Roth, and L. Ji Synergistic Tumor Suppression by Coexpression of FUS1 and p53 Is Associated with Down-regulation of Murine Double Minute-2 and Activation of the Apoptotic Protease-Activating Factor 1-Dependent Apoptotic Pathway in Human Non-Small Cell Lung Cancer Cells Cancer Res., January 15, 2007; 67(2): 709 - 717. [Abstract] [Full Text] [PDF]

				K. Ueda, H. Kawashima, S. Ohtani, W.-G. Deng, M. Ravoori, J. Bankson, B. Gao, L. Girard, J. D. Minna, J. A. Roth, et al. The 3p21.3 Tumor Suppressor NPRL2 Plays an Important Role in Cisplatin-Induced Resistance in Human Non-Small-Cell Lung Cancer Cells Cancer Res., October 1, 2006; 66(19): 9682 - 9690. [Abstract] [Full Text] [PDF]

				X. Zhang, R. M. Cheung, R. Komaki, B. Fang, and J. Y. Chang Radiotherapy Sensitization by Tumor-Specific TRAIL Gene Targeting Improves Survival of Mice Bearing Human Non-Small Cell Lung Cancer Clin. Cancer Res., September 15, 2005; 11(18): 6657 - 6668. [Abstract] [Full Text] [PDF]

				F. Teraishi, S. Wu, J. Sasaki, L. Zhang, H.-B. Zhu, J. J. Davis, and B. Fang P-Glycoprotein-Independent Apoptosis Induction by a Novel Synthetic Compound, MMPT [5-[(4-Methylphenyl)methylene]-2-(phenylamino)-4(5H)-thiazolone] J. Pharmacol. Exp. Ther., July 1, 2005; 314(1): 355 - 362. [Abstract] [Full Text] [PDF]

				M. Nishizaki, J.-i. Sasaki, B. Fang, Edward. N. Atkinson, J. D. Minna, J. A. Roth, and L. Ji Synergistic Tumor Suppression by Coexpression of FHIT and p53 Coincides with FHIT-Mediated MDM2 Inactivation and p53 Stabilization in Human Non-Small Cell Lung Cancer Cells Cancer Res., August 15, 2004; 64(16): 5745 - 5752. [Abstract] [Full Text] [PDF]

				N. K. Sah, A. Munshi, T. Nishikawa, T. Mukhopadhyay, J. A. Roth, and R. E. Meyn Adenovirus-mediated wild-type p53 radiosensitizes human tumor cells by suppressing DNA repair capacity Mol. Cancer Ther., November 1, 2003; 2(11): 1223 - 1231. [Abstract] [Full Text] [PDF]

				R. Danesi, F. De Braud, S. Fogli, T. M. De Pas, A. Di Paolo, G. Curigliano, and M. Del Tacca Pharmacogenetics of Anticancer Drug Sensitivity in Non-Small Cell Lung Cancer Pharmacol. Rev., March 1, 2003; 55(1): 57 - 103. [Abstract] [Full Text] [PDF]