1. 188Re-HYNIC-trastuzumab enhances the effect of apoptosis induced by trastuzumab in HER2-overexpressing breast cancer cells
- Author
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Ping Fang Chiang, Wuu Jyh Lin, Chung Hsin Yeh, Po Ching Cheng, Ting Wu Chuang, and Tsai Yueh Luo
- Subjects
Oncology ,medicine.medical_specialty ,Programmed cell death ,Receptor, ErbB-2 ,Colorectal cancer ,medicine.medical_treatment ,Cell ,Antineoplastic Agents ,Apoptosis ,Breast Neoplasms ,Antibodies, Monoclonal, Humanized ,Trastuzumab ,Cell Line, Tumor ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,skin and connective tissue diseases ,Cytotoxicity ,neoplasms ,Membrane Potential, Mitochondrial ,Radioisotopes ,business.industry ,Nicotinic Acids ,Dose-Response Relationship, Radiation ,General Medicine ,Radioimmunotherapy ,Flow Cytometry ,medicine.disease ,Hydrazines ,Rhenium ,medicine.anatomical_structure ,Cancer cell ,Cancer research ,Radiopharmaceuticals ,Colorectal Neoplasms ,business ,medicine.drug - Abstract
The development of radioimmunotherapy has provided an impressive alternative approach in improving trastuzumab therapy. However, the mechanisms of trastuzumab and radiation treatment combined to increase therapeutic efficacy are poorly understood. Here, we try to examine the efficacy of cytotoxicity and apoptosis induction for (188)Re-HYNIC-trastuzumab in cancer cell lines with various levels of Her2.Fluorescence flow cytometry was used to detect the alterations of apoptosis induction after (188)Re-HYNIC-trastuzumab treatment in two breast cancer cell lines with different levels of HER2 (BT-474 and MCF-7) and a colorectal carcinoma cell line (HT-29) for control.Our results indicated that (188)Re-HYNIC-trastuzumab led to cell death of breast cancer cells specifically in HER2 level-dependent and radioactivity dose-dependent fashions. In BT-474 cells, 370 kBq/ml of (188)Re-HYNIC-trastuzumab enhanced the cytotoxicity to a level nearly 100-fold that of trastuzumab-alone treatment. The results also revealed that the mitochondria-dependent pathway attenuated irradiation-induced apoptosis in HER2-expressing breast cancer cells after (188)Re-HYNIC-trastuzumab treatment. In contrast, only after 48 h of (188)Re-HYNIC-trastuzumab treatment, BT-474 cells exhibited typical apoptotic changes, including exposure of phospholipid phosphatidylserine on the cell surface, or fragmented DNA formation, in a radioactivity dose-dependent manner.Briefly, our study demonstrates that (188)Re-labeled HYNIC-trastuzumab not only enhances cell death in a radioactivity dose-dependent fashion, but may also prolong the effects of apoptosis involved with the mitochondria-dependent pathway in HER2-overexpressing breast cancer cells. It is possible that the (188)Re-HYNIC-trastuzumab treatment induced a second round of apoptosis to prolong the effects of cell kill in these cancer cells. These data revealed that (188)Re-HYNIC-trastuzumab has the potential for use as a therapeutic radiopharmaceutical agent in HER2-overexpressing breast cancer cell treatment.
- Published
- 2014
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