Cooperative therapeutic effects of herpes simplex virus thymidine kinase gene/ganciclovir system and chemotherapeutic agents on prostate cancer in vitro
| Autor: | Yajun Xiao, Ping Xiong, Fuqing Zeng, Wei Feng, Gongcheng Lu, Yifei Xing, Jun Zhao |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Ganciclovir
Male viruses Suramin Biomedical Engineering Antineoplastic Agents Biology Transfection Biochemistry Antiviral Agents Thymidine Kinase Biomaterials chemistry.chemical_compound Cell Line Tumor Genetics medicine Humans Simplexvirus MTT assay RNA Messenger Cisplatin Genes Transgenic Suicide Prostatic Neoplasms Genetic Therapy Molecular biology Cell killing chemistry Apoptosis Cancer cell Cancer research Trypan blue medicine.drug |
| Zdroj: | Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban. 26(5) |
| ISSN: | 1672-0733 |
| Popis: | The killing effects of herpes simplex virus thymidine kinase gene/ganciclovir (HSV-tk/GCV) approach by the addition of several commonly clinical chemotherapeutic agents on hormone refractory prostate cancer (HRPC) cells PC-3m were investigated. After transferring of the HSV-tk gene into PC-3m cells, mRNA and protein expression of HSV-tk was detected by reverse-transcript polymerase chain reaction (RT-PCR) and strept avidin-biotin complex (SABC) immunohistochemical method. The killing effect of GCV, cisplatin (CDDP), etoposide (VP-16), vincristine (VCR), methotrexate (MTX), 5-fluorouracil (5-Fu), and suramin on PC-3m cells was evaluated by morphological assessment analysis, trypan blue exclusion assay and MTT assay respectively. Additionally, the cooperative effect of HSV-tk/GCV system combined with the above agents on the target cancer cells was determined by MTT. Furthermore, apoptosis and necrosis induced by GCV plus 5-Fu or suramin was analyzed by flow cytometry (FCM). The results showed that that there was HSV-tk mRNA and protein expression in pDR2-tk plasmid transduced PC-3m cell. Combination of GCV with VP-16, VCR, 5-Fu or suramin led to an enhanced cellular killing effect, but with CDDP resulted in a reduced one and with MTX in an approximate one. FCM revealed that synergistic use of GCV and 5-fu or suramin resulted in a rather large proportion of apoptosis and necrosis with the apoptosis index being 36.38 % and 35.51 %, and the proportion of necrosis being 33.05 % and 28.87 %, respectively. In conclusion, HSV-tk/CGV approach by addition of certain clinical available chemotherapeutic drugs brings on statistically significant enhanced cell killing over single-agent treatment. Our results highlight the potential for such new combination therapies for future treatments of HRPC. |
| Databáze: | OpenAIRE |
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