Seong-Ho Hong1, Jae-Ho Lee1, Hu-Lin Jiang2, Ji-Eun Kim1, Ah Young Lee1, Sanghwa Kim3, Chong-Su Cho4, Myung-Haing Cho5. 1. Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea. 2. State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, P.R. China. 3. Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea Graduate Group of Tumor Biology, Seoul National University, Seoul, Republic of Korea. 4. Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea. 5. Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea Graduate school of Convergence Science and Technology, Seoul National University, Suwon, Republic of Korea Graduate Group of Tumor Biology, Seoul National University, Seoul, Republic of Korea Advanced Institute of Convergence Technology, Seoul National University, Suwon, Republic of Korea Institute of GreenBio Science Technology, Seoul National University, Pyeongchang-gun, Ganghon-do, Republic of Korea mchotox@snu.ac.kr.
Abstract
BACKGROUND/AIM: Lung cancer has the highest mortality rate among cancers and current therapies are not efficient. Therefore, novel therapeutic methods are urgently needed. Here, we examined the effectiveness of simultaneous Akt1 inhibition and Pdcd4 over-expression using a dual expression system in suppressing tumorigenesis in K-ras(LA1) mice (a lung cancer model). MATERIALS AND METHODS: An shRNA targeting Akt1 (shAkt1) and cDNA of programmed cell death protein 4 (Pdcd4) were inserted into a dual expression vector (shAkt1+Pdcd4). A sorbitol diacrylate-polyethylenimine (SDA-PEI) carrier was used because of low toxicity and high transfection efficiency. Aerosolized SDA-PEI/shAkt1+Pdcd4 complex was delivered to the mice twice a week for 4 weeks using a nose-only exposure inhalation chamber. RESULTS: Simultaneous Akt1 inhibition and Pdcd4 over-expression synergistically induced potent antitumor effect. Analysis revealed significant reduction in lung tumor number. CONCLUSION: Dual expression of shAkt1 and Pdcd4 effectively suppresses lung tumorigenesis. Copyright
BACKGROUND/AIM: Lung cancer has the highest mortality rate among cancers and current therapies are not efficient. Therefore, novel therapeutic methods are urgently needed. Here, we examined the effectiveness of simultaneous Akt1 inhibition and Pdcd4 over-expression using a dual expression system in suppressing tumorigenesis in K-ras(LA1) mice (a lung cancer model). MATERIALS AND METHODS: An shRNA targeting Akt1 (shAkt1) and cDNA of programmed cell death protein 4 (Pdcd4) were inserted into a dual expression vector (shAkt1+Pdcd4). A sorbitol diacrylate-polyethylenimine (SDA-PEI) carrier was used because of low toxicity and high transfection efficiency. Aerosolized SDA-PEI/shAkt1+Pdcd4 complex was delivered to the mice twice a week for 4 weeks using a nose-only exposure inhalation chamber. RESULTS: Simultaneous Akt1 inhibition and Pdcd4 over-expression synergistically induced potent antitumor effect. Analysis revealed significant reduction in lung tumor number. CONCLUSION: Dual expression of shAkt1 and Pdcd4 effectively suppresses lung tumorigenesis. Copyright