关键词: 肿瘤恶病质, 阿利吉仑, 炎性反应, 氧化应激, 自噬溶酶体途径

Abstract: Objective To investigate the effect of ASK on cancer cachexia and its associated mechanism.Methods BALB/c mices were randomly assigned into control group (Con), cancer cachexia group (CA) and ASK intervenient group. Murine colon adenocarcinoma C26 cells were inoculated subcutaneously into mices to induce cachexia. The ASK intervenient group were respectively gavaged with ASK 10 mg /(kg?d) on day 6 and 12(AP and AT group) after injection.Body weight ,spontaneous activity and tumor growth were monitored daily. amples were collected on day 20 and ELISA,colorimetric method,Real-time PCR and Western blot were applied to examincorrelative indexes.Results ASK inhibted the growth of tumor,attenuated the loss of body mass ,increased gastrocnemius weight and its myofiber cross-sectional area and spontaneous activity. Compared with Con group,the levels of renin and angiotensinⅡ in serum and the levels of TNF-α,IL-6 in serum and gastrocnemius of mice in CA group were significantlyhigther(P<0.05); The level of MDA in mice gastrocnemius of CA group was increased and the levels of SOD,GSH-Px were reduced(P<0.05);The mRNAs and proteins expression of Binp3,LC3,Beclin1 in mice gastrocnemius of CA group were upregulated,the ratio of LC3-Ⅱ/LC3-Ⅰwas increased(P<0.05).These indicators change were attenuated by ASK in AT and AP group,and the effect of AP group was superior to that in AT group(P<0.05).Conclusions The effect of ASK alleviating cancer cachexia may be related to inhibitrennin-angiotensin system,thus reduce the oxidative and inflammatory burden, and which in turn to suppress autophagy- lysosome pathway.

Key words: cancer cachexia, aliskiren, inflammation, oxidative stress, autophagy-lysosome pathway