Astaxanthin Supplementation Assists Sorafenib in Slowing Skeletal Muscle Atrophy in H22 Tumor‐Bearing Mice via Reversing Abnormal Glucose Metabolism

Abstract

ScopeCachexia, which is often marked by skeletal muscular atrophy, is one of the leading causes of death in cancer patients. Astaxanthin, a carotenoid obtained from marine organisms that can aid in the prevention and treatment of a variety of disorders. In this study, to assess whether astaxanthin ameliorates weight loss and skeletal muscle atrophy in sorafenib‐treated hepatocellular carcinoma mice is aimed.Methods and resultsH22 mice are treated with 30 mg kg−1 day−1 of sorafenib and 60 mg kg−1 day−1 of astaxanthin by gavage lasted for 18 days. Sorafenib does not delay skeletal muscle atrophy and weight loss, although it does not reduce tumor burden. Astaxanthin dramatically delays weight loss and skeletal muscle atrophy in sorafenib‐treating mice, without affecting the food intake. Astaxanthin inhibits the tumor glycolysis, slows down gluconeogenesis, and improves insulin resistance in tumor‐bearing mice. Astaxanthin increases glucose competition in skeletal muscle by targeting the PI3K/Akt/GLUT4 signaling pathway, and enhances glucose utilization efficiency in skeletal muscle, thereby slowing skeletal muscle atrophy.ConclusionThe findings show the significant potential of astaxanthin as nutritional supplements for cancer patients, as well as the notion that nutritional interventions should be implemented at the initiation of cancer treatment, as instead of waiting until cachexia sets in.

Astaxanthin slows down skeletal muscle atrophy in H22 tumor-bearing mice during sorafenib treatment by modulating the gut microbiota

“…10 In addition, astaxanthin slowed down skeletal muscle atrophy and weight loss in tumor-bearing mice during sorafenib treatment. 11 It is noteworthy that we also detected significant changes in the composition of the gut microbiota in mice who received astaxanthin supplementation. 10 Numerous studies in recent years have revealed that gut microbiota plays a key role in cancer-associated skeletal muscle atrophy.…”

Dietary supplementation with astaxanthin enhances anti-tumor immune response and aids the enhancement of molecularly targeted therapy for hepatocellular carcinoma

“…The findings of our previous study have provided confirmation that the inclusion of astaxanthin as a dietary supplement during sorafenib treatment yields significant efficacy in the inhibition of tumor progression. 19 The observed phenomenon is likely to be associated with the augmented antitumor immune response elicited by astaxanthin. Indeed, there have been reports indicating that astaxanthin plays a role in inhibiting the cell cycle of tumor cells and promoting apoptosis.…”

“…Mice were inoculated with H22 tumor cells subcutaneously in the right axilla after one week of adaptive rearing to construct the H22 tumor-bearing mice, as detailed in our previous report. 19 When the mice subcutaneous tumor models grew to about 100 mm 3 , the mice were randomly divided into four groups ( n = 8). The experimental groups were: (1) model group (M group, n = 8), which was given 0.5% sodium carboxymethyl cellulose administered by gavage daily; (2) sorafenib group (S group, n = 8), which was given 30 mg kg −1 of sorafenib administered by gavage daily; (3) astaxanthin group (A group, n = 8), which was given 60 mg kg −1 of astaxanthin administered by gavage daily; (4) sorafenib combined with Astaxanthin group (SA group, n = 8), which was given 30 mg kg −1 of sorafenib treatment and 60 mg kg −1 of astaxanthin administered by gavage daily.…”

“…RNA was isolated from tumor tissue using the Trizol (Sangon Biotechnology Co., China) reagent as directed by the manufacturer. 19 The purity and concentration of the extracted RNA were measured using the Nanodrop 2000 (Thermo Fisher, USA). Additionally, RNA integrity was confirmed through the utilization of agarose gel electrophoresis (AGE).…”

“…[16][17][18] A recent study conducted by our research group has validated that the dietary supplement of astaxanthin for mice with hepatocellular carcinoma undergoing sorafenib treatment can augment the drug's anti-tumor effects and ameliorate cachexia symptoms, including skeletal muscle atrophy and weight loss in tumor-bearing mice. 19 However, the potential of astaxanthin as an immunomodulator to enhance the antitumor immune response of the molecularly targeted drug sorafenib and the specific mechanism by which it augments the antitumor effects of the drug remain unknown.…”