Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat, India.
Drug Dev Res. 2024 Aug;85(5):e22246. doi: 10.1002/ddr.22246.
Tilorone dihydrochloride (tilorone) is an orally active interferon inducer with anticancer effects. The present study aimed to evaluate the anticancer effects of tilorone in breast cancer. MTT assay was done to measure the proliferation of MCF-7 and MDA-MB-231 breast cancer cells after treatment with tilorone. Mammary carcinogenesis was induced by subcutaneous injection (35 mg/kg, 0.5 mL) of dimethylbenz[a]anthracene (DMBA) in mammary pads of Sprague Dawley (SD) rats. Tumors were allowed to grow for 16 weeks till their sizes reached to 550-700 mm, and then treated with 10 and 20 mg/kg of tilorone and standard drug doxorubicin (4 mg/kg) twice a week for 3 weeks. Normal and disease-control animals received normal saline. Tumor volumes and body weights were measured. Tumors were isolated to measure the levels of interferon-β (IFN-β), vascular endothelial growth factor-A (VEGF-A), P53 and inflammatory markers by enzyme-linked immunosorbent assay (ELISA). Serum biochemistry, lipid peroxidation (LPO) and antioxidant enzymes were measured by standard methods. Histopathology and immunohistochemistry (IHC) of P53 was done in tumor sections. Tilorone reduced the proliferation of MCF-7 and MDA-MB-231 cells with IC concentrations at 34.08 µM and 14.27 µM, respectively. Tilorone treatment showed reduced tumor volume, and increased survival with no significant changes in the body weights. Tilorone treatment also decreased levels of inflammatory markers and VEGF-A and increased IFN-β and P53 levels. Further, treatment with tilorone also decreased LPO and increased antioxidants levels. Histopathology of tumor sections showed normalizing morphology of treated animals. IHC of tumor sections showed increased levels of P53. In conclusion, tilorone has potential anticancer effects against breast cancer.
盐酸替洛隆（替洛隆）是一种具有抗癌作用的口服活性干扰素诱导剂。本研究旨在评估替洛隆在乳腺癌中的抗癌作用。用 MTT 法测定替洛隆处理 MCF-7 和 MDA-MB-231 乳腺癌细胞后的增殖情况。通过在乳腺垫皮下注射二苯并[a]蒽（DMBA）（35mg/kg，0.5mL）诱导 Sprague Dawley（SD）大鼠乳腺癌发生。肿瘤允许生长 16 周，直到其大小达到 550-700mm，然后用 10 和 20mg/kg 的替洛隆和标准药物阿霉素（4mg/kg）每周两次治疗 3 周。正常和疾病对照动物接受生理盐水。测量肿瘤体积和体重。分离肿瘤以通过酶联免疫吸附试验（ELISA）测量干扰素-β（IFN-β）、血管内皮生长因子-A（VEGF-A）、P53 和炎症标志物的水平。通过标准方法测量血清生化、脂质过氧化（LPO）和抗氧化酶。对肿瘤切片进行组织病理学和免疫组织化学（IHC）分析 P53。替洛隆降低 MCF-7 和 MDA-MB-231 细胞的增殖，IC 浓度分别为 34.08µM 和 14.27µM。替洛隆治疗可降低肿瘤体积，提高存活率，体重无明显变化。替洛隆治疗还降低了炎症标志物和 VEGF-A 的水平，增加了 IFN-β 和 P53 的水平。此外，替洛隆治疗还降低了 LPO 并增加了抗氧化剂的水平。肿瘤切片的组织病理学显示治疗动物的形态正常化。肿瘤切片的 IHC 显示 P53 水平升高。总之，替洛隆对乳腺癌具有潜在的抗癌作用。
