Giảm thiểu tình trạng teo cơ vân trong chứng suy mòn ung thư nhờ d-myo-inositol 1,2,6-triphosphate

Cancer Chemotherapy and Pharmacology - Tập 64 - Trang 517-527 - 2008
S. T. Russell1, P. M. A. Siren2, M. J. Siren2,3, M. J. Tisdale1
1Nutritional Biomedicine, School of Life and Health Sciences, Aston University, Birmingham, UK
2Bioneris Ab, IAM, Stockholm, Sweden
3JGK Memorial Research Library and Laboratory, Helsinki, Finland

Tóm tắt

Mục đích nghiên cứu là xác định hiệu quả của tác nhân liên kết kim loại dạng đa anion d-myo-inositol-1,2,6-triphosphate (alpha trinositol, AT) và ester hexanoyl của nó (HAT) trong việc điều trị tình trạng suy nhược cơ thể do ung thư (cachexia). Tác dụng chống suy mòn được đánh giá trên mô hình khối u MAC16. Cả AT và HAT đều làm giảm lượng cơ thể bị mất thông qua việc tăng khối lượng xác không mỡ nhờ cải thiện tổng hợp protein và giảm phân hủy protein trong cơ bắp. Việc giảm phân hủy protein có liên quan đến sự giảm hoạt động của con đường phân huỷ protein ubiquitin-proteasome và caspase-3 và -8. Tổng hợp protein đã được cải thiện nhờ vào việc giảm sự phosphoryl hóa tự động tăng cao của protein kinase phụ thuộc RNA hai mạch, và yếu tố khởi đầu eukaryotic 2α, cùng với sự phosphoryl hóa quá mức của protein liên kết eIF4E và phosphoryl hóa giảm của yếu tố kéo dài eukaryotic 2. Trong môi trường nuôi cấy tế bào, AT hoàn toàn ngăn chặn sự phân hủy protein trong myotube chuột bị kích thích bởi cả yếu tố gây phân hủy protein và angiotensin II. Những kết quả này cho thấy AT là một tác nhân điều trị mới có tiềm năng làm giảm tình trạng suy mòn cơ bắp ở bệnh nhân ung thư.

Từ khóa

#chứng suy mòn ung thư #d-myo-inositol-1 #2 #6-triphosphate #teo cơ vân #tổng hợp protein #phân hủy protein

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