Mối liên hệ giữa các protein liên quan đến chuyển hóa ung thư với sự hình thành ung thư miệng - những chỉ dẫn cho việc hóa dự phòng và tăng cường chuyển hóa của ung thư biểu mô vảy miệng?

Journal of Translational Medicine - Tập 12 - Trang 1-21 - 2014
Martin Grimm1, Marcel Cetindis1, Max Lehmann1, Thorsten Biegner2, Adelheid Munz1, Peter Teriete3, Wiebke Kraut1, Siegmar Reinert1
1Department of Oral and Maxillofacial Surgery, University Hospital Tuebingen, Tuebingen, Germany
2Department of Pathology, University Hospital Tuebingen, Tuebingen, Germany
3Cancer Research Center, Sanford-Burnham Medical Research Institute, La Jolla, USA

Tóm tắt

Chuyển hóa khối u là một yếu tố quan trọng đối với sự phát sinh của ung thư biểu mô vảy miệng (OSCC). Sự biểu hiện của IGF-R1, các protein liên quan đến quá trình đường phân (GLUT-1, HK 2, PFK-1, LDHA, TKTL1), các enzyme hô hấp ti thể (SDHA, SDHB, ATP synthase) đã được phân tích trên mô niêm mạc miệng bình thường (n = 5), tổn thương tiền ung thư miệng (tăng sinh đơn giản, n = 11; loạn sản biểu mô vảy, SIN I-III, n = 35), và mẫu bệnh phẩm OSCC (n = 42) bằng phương pháp hóa mô miễn dịch và phân tích phản ứng chuỗi polymerase thời gian thực (qPCR) trên các dòng tế bào OSCC. Các protein liên quan đến chuyển hóa có mối liên hệ với hoạt động tăng sinh (Ki-67) và các đặc tính chết theo chương trình (phân tích TUNEL) trong OSCC. Đặc hiệu của các kháng thể được xác nhận bằng phương pháp western blot trên các dòng tế bào ung thư. Sự biểu hiện của IGF-R1, các protein liên quan đến đường phân (GLUT-1, HK 2, LDHA, TKTL1), và các enzyme hô hấp ti thể (SDHA, SDHB, ATP synthase) đều tăng đáng kể trong quá trình phát sinh của OSCC. Các vùng có hoạt động chuyển hóa cao trong OSCC có mối liên hệ mạnh mẽ với các tế bào ung thư đang phân chia (Ki-67+) mà không có dấu hiệu của sự chết theo chương trình (phân tích TUNEL). Nghiên cứu này cung cấp bằng chứng đầu tiên về sự biểu hiện của IGF-R1, các protein liên quan đến đường phân GLUT-1, HK 2, PFK-1, LDHA, và TKTL1, cũng như các enzyme ti thể SDHA, SDHB, và ATP synthase trong quá trình hình thành các bước nhiều giai đoạn của OSCC. Chuyển hóa glucose liên quan đến thiếu oxy và các đặc điểm phosphoryl oxi ti thể đều có liên quan đến sự phát sinh của OSCC. Tình trạng toan hóa và OXPHOS có thể thúc đẩy sự chuyển hóa về con đường pentose phosphate (PPP). Do đó, việc ức chế PPP, quá trình đường phân, và các liệu pháp chống ti thể nhắm mục tiêu (tạo ROS) bằng các hợp chất tự nhiên hoặc các dẫn xuất vitamin tổng hợp có thể đóng vai trò là chất nhạy cảm cho sự chết theo chương trình trong các tế bào ung thư được trung gian bởi các liệu pháp hỗ trợ trong OSCC.

Từ khóa

#chuyển hóa khối u #ung thư biểu mô vảy miệng #hóa dự phòng #protein liên quan đến chuyển hóa #tế bào ung thư

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