Combined use of iguratimod with pyrrolidine dithiocarbamate alleviates cancer cachexia in a mouse model

Abstract

Objective To observe the effect of the combined use of iguratimod (T614) and pyrrolidine dithiocarbamate (PDTC) on animal cancer cachexia model. Methods Male BALB/C mice bearing colon 26 adenocarcinoma for 9 days served as models of cancer cachexia. Seven days after the treatment,body weight and gastrocnemius muscle were documented. Biochemical indicators, serum interleukin-6 (IL-6) , and tumor necrosis factor-α (TNF-α) levels were evaluated. The expression of nuclear factor-κB ( NF-κB ) in tumor was detected by using immunohistochemistry. Results The IL-6 levels in cachexia group, T614 group, PDTC group and T614 + PDTC group were (93. 72 ± 11. 20), (81.11 ± +11.08),(79. 25 ±9. 91) and (53. 60 ± 10. 5) ng/L, and those of TNF-a were (128. 70 ± 33. 41) , (90. 16 ±11. 57) , (99. 51 ± 15. 25) and (75. 45 ± 12. 48) ng/L, respectively. The IL-6 and TNF-α levels in T614 group, PDTC group and T614 + PDTC group were significantly lower than in cachexia group ( all P ＜0. 05). The expression of NF-kB was significantly down-regulated in T614 group, PDTC group and T614 +PDTC group as compared with cachexia group (P ＜ 0. 05). Conclusion Inhibition of NF-kB can attenuate the development of cachexia in colon 26 tumor bearing mice. These findings suggest that a therapeutic approach combining T614 with PDTC does have complementary effect in improving outcomes of cancer cachexia. Key words: Cachexia; Nuclear factor-κB; Pyrrolidine dithiocarbamate; Iguratimod