การจัดการระบบเอนโดแคนนาบินอยด์สำหรับการรักษาโรคมะเร็ง: โดยใช้ปลาม้าลายเป็นต้นแบบ

บทคัดย่อ

Colorectal cancer (CRC) is one of the most frequent and deadly forms of cancer, especially due to its ability to metastasize. Current cancer treatments have shown to be unable to block tumour progression, and thus new and more efficient therapeutic treatments are needed. Cannabinoids have long been used as palliative in cancer treatment and recently have been proven to have anti-tumorigenic properties. Narachidonoyl ethanolamide (anandamide, AEA) is an endocannabinoid that inhibits cell growth and induces cell death in several types of cancer. In our study, we investigate the anti-oncogenic properties of AEA on CRC, using a zebrafish xenograft approach and the HCT116 human colon carcinoma cells. We observed that in zebrafish treated with AEA, the tumour volume was smaller as well as the vascularization around the tumour. These effects were highly specific of the AEA action, as larvae treated with AM251, an AEA inhibitor, behave similarly to the controls. The ability of AEA to reduce the insurgence and spread of metastasis from the main tumour to the rest of the body was also clearly evidenced. The preliminary results of the seq RNA associate with specific proteomic analyses suggest that AEA works reducing malignant cell proliferation while no changes in the signals involved in apoptosis as well as in autophagy were recorded. The lack of apoptosis/ autophagy was confirmed by in vitro studies on HCT116 human cell. Altogether, our results highlight the importance of zebrafish xenografts in the study of anti-oncogenic molecules and suggested the pathways controlled by AEA in CRC cells.

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