Gynecologic Pathology
Lila Siavoshinia; Mostafa Jamalan; Majid Zeinali; Aminollah Pourshohod; Mahdie Koushki; Bahman Moradipoodeh; Ghorban Mohammadzadeh
Abstract
Background & objectives: Overexpression of human epidermal growth factor receptor 2 (HER2) causes cell transformation and development of various types of malignancies. Idarubicin is an effective anti-neoplastic drug but specific delivery of it to the targeted cells is still a great challenge. Affibody ...
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Background & objectives: Overexpression of human epidermal growth factor receptor 2 (HER2) causes cell transformation and development of various types of malignancies. Idarubicin is an effective anti-neoplastic drug but specific delivery of it to the targeted cells is still a great challenge. Affibody as a cost-effective peptide molecule with low molecular weight has a high affinity for HER2 receptors. Breast and ovarian cancers as wide speared types of malignancies are associated with high expression of HER2. In the current study, we assessed the cytotoxic effects of idarubicin-ZHER2 affibody conjugate on the positive-HER2 cancer cell lines. Methods: The cytotoxic effects of constructed idarubicin-ZHER2 affibody conjugate on the SK-BR-3, SK-OV-3, and MCF-7 cells with various levels of HER2 expression were evaluated by MTT assay after 48 hours of incubation time. Results: Idarubicin showed a potent and dose-dependent cytotoxic effect against all treated cell lines while the SK-OV-3 cells were significantly more sensitive. The dimeric form of the ZHER2 affibody molecule showed a mild effect on the cell viability of all treated cells at its optimum concentration. The constructed Idarubicin-ZHER2 affibody conjugate decreased the viability of SK-OV-3 cells at its optimal concentration, more efficiently and specifically than other treated cells. Conclusion: The ZHER2-affibody conjugate of idarubicin has a more specific cytotoxic effect compared with idarubicin alone against HER2-overexpressing ovarian cancerous cells. It appears the ZHER2-affibody conjugate of idarubicin has great potential to be implicated as an innovative anti-cancer agent in future clinical trials in patients with HER2-overexpressing ovarian cancer.
Biochemistry
Maryam Karimi; Hossein Babaahmadi-Rezaei; Ghorban Mohammadzadeh; Mohammad-Ali Ghaffari
Abstract
Background and objective: According to reports, a serine protease inhibitor (Maspin) suppresses metastasis, invasion and angiogenesis in breast and prostate cancers. Silibinin is a natural polyphenolic flavonoid with anti-cancer activity. We assessed the effects of silibinin on cell viability, maspin ...
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Background and objective: According to reports, a serine protease inhibitor (Maspin) suppresses metastasis, invasion and angiogenesis in breast and prostate cancers. Silibinin is a natural polyphenolic flavonoid with anti-cancer activity. We assessed the effects of silibinin on cell viability, maspin and ERα gene expression in MCF-7 cell line. Methods: The human MCF-7 breast cancer cell line was cultured in Dulbecco’s Modified Eagle’s Medium (DMEM) and treated with different concentrations of silibinin (100-600 μg/mL) for 24, 48 and 72 hours. The cytotoxic effect of silibinin on MCF-7 viability was determined using Methyl-Thiazolyl-Tetrazolium (MTT) assay by IC50 determination. The fold changes of Maspin and ERα expression were determined by reverse-transcription real-time Polymerase Chain Reaction (PCR). All experiments on the cells were performed in triplicates. Results: The maximum inhibitory effect of silibinin on cell viability was observed at 600 μg/mL after 72-hour incubation (p = 0.001). Incubation of the cells with silibinin for 48 and 72 hours significantly decreased IC50 values to 250 and 207 μg/mL (p = 0.005 and p= 0.006), respectively. The expression of maspin and ERα in the treated cells compared to controls was significantly decreased following treatment with different concentrations of silibinin during a 24-hour period. Conclusions: Silibinin reduces both maspin and ERα gene expression in MCF-7 cell line. The therapeutic effect of silibinin on the treatment of breast cancer may be mediated by the reduction of ERα expression. For verifying this hypothesis and the possible therapeutic implication of silibinin on breast cancer, further studies in this direction are necessary.