Abstract
Effective delivery of chemotherapeutic agents to tumors is a critical objective of improved cancer therapy. Traditional antiangiogenic therapy aims at eradicating tumor blood vessels, but the subsequently reduced blood perfusion may limit the drug amount delivered into the tumor and potentially lead to tumor hypoxia, which has been proved to be unable to meet the therapeutic expectations. “Shexiang Baoxin Pill” (SBP) is a well-known traditional Chinese medicine (TCM) used in clinical treatment of cardiovascular diseases, which has the pharmacological effect of pro-angiogenesis demonstrated recently. In this study, we disclosed our finding that SBP could enhance the effective treatment performance of gemcitabine (GEM) while minimizing the toxic side effects caused by GEM. Mechanistically, SBP increased tumor angiogenesis, blood perfusion, vascular permeability, and vessel dilation, which subsequently favored the delivery of GEM to the tumor lesion. Moreover, combined treatment with SBP and GEM could modify tumor microenvironment and consequently overcome multidrug resistance, and this combination therapy is also suitable for combination of SBP with some other chemotherapeutic drugs as well. These results suggest that combining SBP with chemotherapeutic agents achieves better treatment efficiency, which can open an avenue for expanding the combined treatment of anti-cancer chemotherapeutic drugs with TCM.
Highlights
Anti-angiogenesis is a targeted therapeutic strategy and was once considered to be an effective treatment for cancers (Wu et al, 2018)
In vivo antitumor activity was evaluated in murine syngeneic Lewis lung carcinoma (LLC) tumor-bearing mice
The control group, all the treatments except the Shexiang Baoxin Pill” (SBP) (32 mg/kg) monotherapy exhibited anti-tumor activity to some degree
Summary
Anti-angiogenesis is a targeted therapeutic strategy and was once considered to be an effective treatment for cancers (Wu et al, 2018). Vascular disrupting agents aim at inducing tumor blood flow shutdown rapidly and selectively, resulting in massive necrosis (Siemann, 2011) They may potentially enhance tumor hypoxia and elevated tumor metastasis, failing to meet the therapeutic expectations (Palumbo et al, 2011). Recent research has reported that promoting tumor angiogenesis and increasing blood flow would potentially improve the effectiveness of anti-tumor therapy (Bridges and Harris, 2015; Villanueva, 2015; Wong et al, 2015, 2016; Yin et al, 2017). This strategy for treating tumors is radically different from the previous methods and is called “vascular promotion therapy” which at the best of our knowledge has been rarely studied so far
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