Phân tích tính tương hỗ trong ức chế các tế bào ung thư vú xâm lấn giữa paclitaxel và thymoquinone

Mohammad Rsool Khazaei1, Maryam Bozorgi1, Mozafar Khazaei1, Alireza Moradi2, Azam Bozorgi3,1
1Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
2Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
3Department of Tissue Engineering, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran

Tóm tắt

Trong thí nghiệm hiện tại, chúng tôi đã đánh giá tác động của điều trị thymoquinone (TQ) và paclitaxel (PTX) đối với sự ức chế tăng trưởng của dòng tế bào MDA-MB-231 thông qua kiểm soát apoptosis/autophagy. Các tế bào MDA-MB-231 đã được tiếp xúc với PTX (0, 25, 50, 75, và 100 nM), TQ (0, 25, 50, 75, và 100 µM), và các kết hợp trong 48 giờ. Sau khi đánh giá MTT, các đường cong mối quan hệ liều và giá trị IC50 đã được tính toán, và tính tương hỗ của các kết hợp đã được đánh giá bằng phần mềm Compusyn. Sau khi điều trị bằng PTX, TQ và các kết hợp tại nồng độ IC50, sự biểu hiện của các gen apoptosis và autophagy đã được đánh giá trong các tế bào. Chương trình GraphPad Prism đã được sử dụng để phân tích dữ liệu, và kiểm định Tukey với p < 0.05 đã được thực hiện. PTX, TQ, và các kết hợp của chúng đã ức chế sự tăng trưởng và khả năng sống sót của tế bào MDA-MB-231 theo liều phụ thuộc. TQ đã giảm nồng độ hiệu quả (IC50) của PTX trong các nhóm điều trị phối hợp. PTX và TQ cho thấy tác dụng đối kháng khi sự tăng trưởng tế bào giảm trên 70%. Tác dụng đối kháng chuyển thành tác dụng cộng tính và tương hỗ khi nồng độ PTX tăng, được chỉ ra bởi sự giảm tăng trưởng tế bào dưới 70%. Sự phối hợp điều trị PTX-TQ đã làm tăng đáng kể biểu hiện của P53 và BAX trong khi giảm biểu hiện của Bcl-2. Hơn nữa, sự kết hợp này cũng làm tăng biểu hiện của Beclin-1, ATG-5, và ATG-7 trong các tế bào đã được điều trị. Nồng độ hiệu quả của TQ và PTX có tác dụng tương hỗ và ức chế các tế bào ung thư vú thông qua việc kích thích apoptosis và autophagy trong điều kiện in vitro.

Từ khóa

#thymoquinone #paclitaxel #MDA-MB-231 #apoptosis #autophagy #ung thư vú

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