Cholecalciferol (Vitamin D3) Ức Chế Tăng Trưởng và Xâm Nhập Bằng Cách Tăng Cường Các Thụ Thể Hạt Nhân và Enzyme 25-Hydroxylase (CYP27A1) Trong Các Tế Bào Ung Thư Tuyến Tiền Liệt Nhân Loại

Springer Science and Business Media LLC - Tập 22 - Trang 275-284 - 2005
Erik J. Tokar1, Mukta M. Webber1
1Departments of Zoology and Medicine, Michigan State University, East Lansing, USA

Tóm tắt

Bằng chứng dịch tễ học cho thấy có mối quan hệ nghịch giữa ung thư tuyến tiền liệt và mức vitamin D trong huyết thanh. Chúng tôi đã khảo sát khả năng của cholecalciferol (vitamin D3), một tiền chất_calcitriol, trong việc ức chế hoặc đảo ngược các thay đổi tế bào liên quan đến chuyển hóa ác tính và xâm lấn, đồng thời khám phá các cơ chế hoạt động của nó. Dòng tế bào biểu mô tuyến tiền liệt RWPE2-W99, có khả năng hình thành các khối u phát triển chậm ở chuột nude, đã được sử dụng vì nó mimics hành vi của phần lớn các loại ung thư tuyến tiền liệt nguyên phát ở người. Cholecalciferol, ở mức độ sinh lý: (i) ức chế sự phát triển phụ thuộc vào điểm bám và không phụ thuộc vào điểm bám; (ii) kích thích sự biệt hóa bằng cách giảm sự biểu hiện vimentin kèm theo giảm tính di động/chemotaxis; (iii) giảm hoạt động MMP-9 và MMP-2 với sự giảm đi kèm về xâm lấn; và (iv) thực hiện tác động của nó bằng cách tăng cường thụ thể vitamin D (VDR), thụ thể retinoid-X α (RXR-α), và thụ thể androgen (AR) theo cách phụ thuộc vào liều. Hơn nữa, chúng tôi thấy rằng các tế bào ung thư tuyến tiền liệt RWPE2-W99, giống như tế bào RWPE-1 (Tokar và Webber. Clin Exp Metast 2005; 22: 265–73), thường xuyên biểu hiện enzyme 25-hydroxylase CYP27A1, mà được tăng cường rõ rệt bởi cholecalciferol. Cholecalciferol có tác động tương tự như calcitriol về tăng trưởng, hoạt động của MMP và VDR. Khả năng của CYP27A1 trong việc xúc tác chuyển đổi cholecalciferol thành 25(OH)D3 và 25(OH)D3 thành calcitriol đã được báo cáo. Các tế bào RWPE2-W99, tương tự như các tế bào RWPE-1, dường như có khả năng hiếm gặp để chuyển đổi địa phương cholecalciferol thành hormone hoạt động calcitriol. Vì nó có thể ức chế các thay đổi tế bào liên quan đến chuyển hóa ác tính và xâm lấn, chúng tôi đề xuất rằng cholecalciferol có thể là một tác nhân hiệu quả cho việc điều trị ung thư tuyến tiền liệt.

Từ khóa

#ung thư tuyến tiền liệt #cholecalciferol #vitamin D3 #MMP #thụ thể vitamin D #CYP27A1

Tài liệu tham khảo

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