S-Adenosylmethionine synergistically enhances the antitumor effect of gemcitabine against pancreatic cancer through JAK2/STAT3 pathway
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Gemcitabine (GEM) has been widely used for pancreatic cancer (PC) treatment but limited by the development of drug resistance. The agents that reverse its resistance and improve the chemo-sensitivity are urgently needed. S-Adenosylmethionine (SAM) is a precursor for polyamine biosynthesis in mammalian cells and plays a key role in biological transmethylation events. It is reported that SAM could be used as a therapeutic reagent for cancer treatments. In this study, we investigated the chemo-sensitization of SAM to potentiate the antitumor effect of GEM in PC. After treating PC cells with GEM and/or SAM, different subsequent experiments were performed. Results showed that SAM plus GEM could significantly inhibit the growth and proliferation of PC cells, and SAM acts synergistically with GEM. The combinative treatment could induce cell apoptosis and inhibit invasion and migration through JAK2/STAT3 inactivation. Inhibition of JAK2/STAT3 pathway significantly enhanced the pro-apoptotic effect of SAM, suggesting the key roles of JAK2/STAT3 in the process. Moreover, co-treatment with GEM and SAM exhibited more efficient inhibition of tumor weight and volume on PANC-1 xenograft mouse model compared to GEM or SAM alone and has no significant effect on the function of the liver and kidney. In general, this study indicated that SAM synergistically enhanced the antitumor effect of GEM against PC through suppressed JAK2/STAT3 pathway, and SAM is applicable as a promising agent to improve the sensitivity of PC to GEM.
KeywordsS-Adenosylmethionine Pancreatic cancer Gemcitabine Synergistically JAK2/STAT3
Author contribution statement
LY, QL, and SGH carried out the main work and drafted the manuscript. BTT and LLX carried out the western blot and immunohistochemistry. LY and BTT carried out the in vivo study. LY and GQG performed the statistical analysis. QL and LY designed the study. All authors read and approved the final manuscript.
The present study was supported by the Program for Medical and health application basic research of Suzhou City (No.SYSD2016042), the Program for Wujiang No.1 People’s Hospital (No.201603).
Compliance with ethical standards
All experiments were approved by the Wujiang No.1 People’s Hospital Ethics Committee.
Conflict of interest
The authors declare that they have no competing interests.
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