Kai Qi1, Yang Li2, Ke Huang3, Xilin Xiong4, Feng Chuchu5, Chi Zhang6, Wenjun Weng7. 1. Department of Pediatric Hematology/Oncology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510120, PR China. Electronic address: briskly@163.com. 2. Department of Pediatric Hematology/Oncology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510120, PR China. Electronic address: drliyang@126.com. 3. Department of Pediatric Hematology/Oncology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510120, PR China. Electronic address: hk01022@sina.com. 4. Department of Pediatric Hematology/Oncology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510120, PR China. Electronic address: kikibear@163.com. 5. Department of Pediatric Hematology/Oncology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510120, PR China. Electronic address: 342003590@qq.com. 6. Department of Pediatric Hematology/Oncology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510120, PR China. Electronic address: chizhang90@163.com. 7. Department of Pediatric Hematology/Oncology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510120, PR China. Electronic address: wengwenjunlin@126.com.
Abstract
BACKGROUND: Arsenic trioxide is effective in the treatment of acute promyelocytic leukemia and is currently in use in clinical trials for the treatment of solid tumor types. Given that arsenic trioxide is able to arrest neuroblastoma cell cycle in the G2/M phase, the present study is, to the best of our knowledge, the first to investigate whether the combination of arsenic trioxide with mitosis-phase-specific antineoplastic agents (vinorelbine or docetaxel) or non-mitosis-phase-specific antineoplastic agents (etoposide or cisplatin) exert synergistic effects in cytotoxicity on the human SK-N-SH neuroblastoma cell line. METHODS: Neuroblastoma cells were either incubated with one of the four drugs individually, or preincubated with arsenic trioxide and then followed by another drug when cell cycle was arrested at the G2/M phase with the highest proportion. RESULTS: The results of the present study revealed that arsenic trioxide potentiated the apoptotic rate of neuroblastoma cells induced by chemotherapeutic drugs. The present study further demonstrated that preincubation with arsenic trioxide followed by a mitosis-phase-specific antineoplastic agent result in a higher cytotoxicity effect compared with a non mitosis-phase-specific antineoplastic agent. Along with the enhanced cytotoxicity in combination group, the cell cycle distribution demonstrated a decreased proportion of G2/M phase in the combination group. CONCLUSION: The in vitro study revealed that the pre-application of arsenic trioxide followed by mitosis-phase-specific antineoplastic agents potentiate the cytotoxic effects on neuroblastoma cells, therefore arsenic trioxide may be a promising therapeutic option for treating neuroblastoma.
BACKGROUND:Arsenic trioxide is effective in the treatment of acute promyelocytic leukemia and is currently in use in clinical trials for the treatment of solid tumor types. Given that arsenic trioxide is able to arrest neuroblastoma cell cycle in the G2/M phase, the present study is, to the best of our knowledge, the first to investigate whether the combination of arsenic trioxide with mitosis-phase-specific antineoplastic agents (vinorelbine or docetaxel) or non-mitosis-phase-specific antineoplastic agents (etoposide or cisplatin) exert synergistic effects in cytotoxicity on the humanSK-N-SH neuroblastoma cell line. METHODS:Neuroblastoma cells were either incubated with one of the four drugs individually, or preincubated with arsenic trioxide and then followed by another drug when cell cycle was arrested at the G2/M phase with the highest proportion. RESULTS: The results of the present study revealed that arsenic trioxide potentiated the apoptotic rate of neuroblastoma cells induced by chemotherapeutic drugs. The present study further demonstrated that preincubation with arsenic trioxide followed by a mitosis-phase-specific antineoplastic agent result in a higher cytotoxicity effect compared with a non mitosis-phase-specific antineoplastic agent. Along with the enhanced cytotoxicity in combination group, the cell cycle distribution demonstrated a decreased proportion of G2/M phase in the combination group. CONCLUSION: The in vitro study revealed that the pre-application of arsenic trioxide followed by mitosis-phase-specific antineoplastic agents potentiate the cytotoxic effects on neuroblastoma cells, therefore arsenic trioxide may be a promising therapeutic option for treating neuroblastoma.