Leukemia Stem-like KG-1a Cells Escape the Synergistic Cytotoxic Effect of Arsenic Trioxide and Aclacinomycin: Regulated By Survivin

Leukemia stem-like KG-1a cells escape the synergistic cytotoxic effect of arsenic trioxide and aclacinomycin: regulated by survivin

Yongbin YE¹ , Xiaojun.XU¹ , Liu Qifa²

Correspondence to: Xiaojun XU. E-mail: doctorxu@163.com

¹Department of Hematology, Zhongshan Hospital of Sun Yat-sen University & Zhongshan City People Hospital, Zongshan 528403

²Department of Hematology, Nanfang Hospital of Southern Medical University, Guangzhou,510515

Abstract AIM OF STUDY: Arsenic trioxide combined with aclacinomycin has a synergistic cytotoxic effect on leukemia stem cell-like cells KG-1a in our pervious study, however, there are still a part of KG-1a cells escaped the synergistic cytotoxicity, survivin may plays in a key role in this process. In this study, we have studied the interaction and mechanism of survivin in regulating leukemia stem-like KG-1a cell escape the synergistic cytotoxic effect of arsenic trioxide and aclacinomycin. MATERIALS AND METHODS: The anti-proliferation effect was detected by CCK-8 and colony-forming assay, protein-protein chip assay was used to analysis the expression level of survivin before and after combination treatment. The induction of apoptosis and cell cycle arrest in KG-1a cell line were detected by FACS, the expression of related signal pathway protein was detected by western blot. RESULTS: The anti-proliferation of KG-1a cells caused by arsenic trioxide or aclacinomycin showed a time- and dose-independent manner. However, protein-protein chip assay showed that the expression of survivin had a significant increase after the combination treatment (p<0.05), but when survivin was suppressed, the apoptosis rate had a more significant increase than the single drug treatment. Meanwhile, more prominent cell cycle arrest was observed in the combination treatment, further study found that suppression of survivin combined with chemotherapy may activate the related apoptosis pathway protein but suppress the PI3K/AKT signal pathway. CONCLUSION: survivin play an important role in regulating leukemia stem cell escape the synergistic cytotoxic effect of arsenic trioxide and aclacinomycin. The mechanism of regulation process may through activate the related apoptosis pathway protein and supperss the PI3K/AKT signal pathway. This study may provide a further benefit for reversing chemotherapy resistant for acute leukemia

Key words: arsenic trioxide,aclacinomycin, Acute leukemia; survivin; chemotherapy resistant