Hyperthermia increases the therapeutic efficacy of survivinT34A in mouse tumor models
Zhi-Mian Li1, Yu-Wei Zhao, Cheng-Jian Zhao
1Sichuan University, Chengdu, China. yhansh@scu.edu.cn
Abstract:
The use of survivinT34A mutant targeted disruption of survivin, the strongest inhibitor of apoptosis protein overexpressed in tumors, has proved a promising strategy for advanced cancers. However, hyperthermia, as a cytotoxic enhancer, regularly activates the expression of survivin to counteract the heat-induced antitumor activity. Here, we investigated the combinational antitumor effect by using liposome-encapsulated mouse survivinT34A and hyperthermia in mouse models. We observed that the combination treatment of surivinT34A and hyperthermia significantly increased the growth inhibition and apoptosis of tumor cells in vitro compared with single treatment or other controls, which was similar to the effect of survivin silencing in combination with hyperthermia. Moreover, the inhibition of tumor growth in vivo was also remarkably enhanced by combination of surivinT34A and hyperthermia when compared with other treatments. Naturally, the tumor tissues in combination treatment presented the larger necrosis-like areas, more apoptotic cells and less microvessel density. Our findings suggest that the antitumor efficacy of survivin disruption can be enhanced by hyperthermia, which might be a new feasible approach for cancer therapy.
Insights
Combining survivinT34A mutant therapy with hyperthermia significantly enhances antitumor effects. This combination therapy increases tumor cell apoptosis and growth inhibition, offering a promising new approach for advanced cancers.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapy
Background:
- Survivin is a key inhibitor of apoptosis protein overexpressed in tumors.
- SurvivinT34A mutant offers a targeted disruption strategy for cancer treatment.
- Hyperthermia can paradoxically increase survivin expression, counteracting its antitumor effects.
Purpose of the Study:
- To investigate the combined antitumor effect of liposome-encapsulated mouse survivinT34A and hyperthermia.
- To evaluate the efficacy of this combination therapy in preclinical mouse models.
Main Methods:
- Liposome-encapsulated mouse survivinT34A was administered in combination with hyperthermia.
- In vitro and in vivo tumor models were used to assess treatment efficacy.
- Tumor growth, apoptosis, necrosis, and microvessel density were analyzed.
Main Results:
- Combination treatment significantly increased tumor cell growth inhibition and apoptosis in vitro.
- In vivo tumor growth inhibition was markedly enhanced by the combination therapy.
- Tumor tissues showed larger necrosis-like areas, increased apoptosis, and reduced microvessel density.
Conclusions:
- Hyperthermia can enhance the antitumor efficacy of survivin disruption.
- The combination of survivinT34A and hyperthermia presents a feasible approach for cancer therapy.
