Background and purpose: With the application of novel agents and immune therapeutic strategies

treatment outcomes of multiple myeloma (MM) patients have dramatically improved including not only rates and depth of response

but also progression-free survival. However

a considerable number of patients become relapsed/refractory cases. Studies revealed that the treatment with cyclic adenosine monophosphate (cAMP) or arsenic trioxide (As

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) might be a promising strategy for MM therapy. The present study aimed to explore the possible effects of cAMP analogue 8-(4-chlorophenylthio) adenosine 3’

5’-cyclic monophosphate (8-CPT-cAMP) combined with As

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on MM cells and its potential mechanisms. Methods: The MM cell line U266 cells were treated with different concentrations of As

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and 8-CPT-cAMP. The proliferation of U266 cells was evaluated through cell counting kit-8 (CCK-8) assay. The synergistic manner of the two agents was determined by calculation of combination index (CI). Meanwhile

flow cytometry was used to analyze the changes of cell cycle distribution and apoptotic rate. Furthermore

Western blot assay was applied to detect expression levels of apoptosis modulator caspase-3 and Bcl-2. Results: After treatment with As

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 and/or 8-CPT-cAMP for 72 and 120 h

the growth inhibition rates of U266 cells in combination groups reached (18.01±0.13)% and (28.01±0.14)%

which were significantly higher than those in As

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or 8-CPT-cAMP alone group ［As

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group: (11.35±0.01)% and (16.01±0.14)%; 8-CPT-cAMP group: (12.26±0.30)% and (15.43±0.23)%; P0.05］. The CI value of As

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combined with 8-CPT-cAMP was higher than one in U266 cells. The apoptotic rates of U266 cells in combination groups were (22.26±0.13)% and (31.03±

0.14)%

which were significantly higher than those in As

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or 8-CPT-cAMP alone group ［As

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group: (10.06±0.01)% and (12.35±0.14)%; 8-CPT-cAMP group: (13.26±0.30) % and (18.76±0.23)%; P0.05］. It was also shown that As

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combined with 8-CPT-cAMP induced degradation of caspase-3 and down-regulated expression of Bcl-2 in U266 cells. Conclusion: The effect of As

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combined with 8-CPT-cAMP on induction of apoptosis in MM cells was stronger than that of single drug

but there was no synergistic effect.