| Summary: | 博士 === 國立中興大學 === 生命科學系所 === 101 === Background:
Advanced or metastatic prostate cancers tend to turn into castration-resistant cancers after hormonal therapy. Most of these cases are characterized by elevated HER2 expression and have poor prognosis. Herceptin (Trastuzumab), a humanized anti-HER2 monoclonal antibody, is widely used for the treatment of patients with HER2-overexpressing breast cancer. However, the application of Herceptin in prostate cancer patients is still controversial. In order to understand whether radioimmunotherapeutic strategy is more effective than immunotherapy by attacking HER2 alone, we labeled the Rhenium-188, a beta emitter, onto Herceptin to evaluate its radioimmunotherapeutic effect on prostate cancer with elevated HER2 expression in vitro and in vivo compared with immunotherapy with Herceptin alone and radiotherapy with Re-188 alone.
Methods:
DU145, an androgen receptor negative prostate cancer cell line with elevated HER2 expression, was used to evaluate the therapeutic effect of the Herceptin labeled with Rhenium-188 (Re-188), a beta emitter. Its effect is evaluated in vitro on cell growth, extent of apoptosis, protein levels as well as in vivo on bio-distribution, tumor growth, apoptosis and protein levels.
Results:
The proliferation of DU145 cells was inhibited after treated with the Re-188 Herceptin (Re-H) in dose- and time-dependent manners but not in the control groups treated with PBS (phosphate buffered saline) and Herceptin alone. The proliferate inhibition and apoptosis were induced after Re-H treatment. The in vivo xenograft study revealed tissue-specific bio-distribution of Re-188 Herceptin, which results in significant decrease of tumor growth and correlated changes of apoptosis-related proteins. Moreover, the level of p35 protein, which responds for cancer cell survival and invasion by activating Cdk5, dramatically decreased after Re-188 Herceptin treatment.
Conclusion:
Our data indicate that Re-188 labeled Herceptin effectively inhibited the growth of DU145 cells compared to the Herceptin- and Re-188-treated cohorts. This implies that targeting Her2 by both radio- and immuno- therapy might be a potential strategy for treating patients with castration-resistant prostate cancer.
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