- 作者: Zhuomin Huang, Shiwen Peng, Jayne Knoff, Sung Yong Lee, Benjamin Yang, Tzyy-Choou Wu,Chien-Fu Hung
- 作者服務機構: Department of Pathology, Johns Hopkins Medical Institutions, Orleans Street, Baltimore, MD, USA
- 中文摘要: --
- 英文摘要:
Background:
Bortezomib, a proteasome inhibitor and suberoylanilide hydroxamic acid (SAHA, also known as Vorinostat), a histone deacetylase inhibitor, have been recognized as potent chemotherapeutic drugs. Bortezomib and SAHA are FDA-approved for the treatment of cutaneous T cell lymphoma and multiple myeloma/mantle cell lymphoma, respectively. Furthermore, the combination of the bortezomib and SAHA has been tested in a variety of preclinical models and in clinical trials and may be ideal for the treatment of cancer. However, it remains unclear how this treatment strategy affects the host immune response against tumors.
Results:
Here, we used a well-defined E6/E7-expressing tumor model to examine how the immune system can be motivated to act against tumor cells expressing tumor antigens. We demonstrate that the combination of bortezomib and SAHA elicits potent antitumor effects in TC-1 tumor-bearing mice. Additionally, we are the first to show that treatment with bortezomib and SAHA leads to tumor-specific immunity by rendering tumor cells more susceptible to killing by antigen-specific CD8+ T cells than treatment with either drug alone.
Conclusions:
The current study serves an important foundation for the future clinical application of both drugs for the treatment of cervical cancer. - 中文關鍵字: --
- 英文關鍵字: Bortezomib, SAHA, Vorinostat, Antitumor, Host immunity