Yuyi Feng DanXia Qiu Yangcheng He Hai Jin Liping Chen Fen Xi Zhiwen Hu Yanlin Xie Yucai Li Minhua Lin Pengxiao Sun Yan He ^* Jianhua Liu ^*

• Department of ultrasound, the second affiliated hospital, school of medicine, south China university of technology., Guangzhou, China

The oxygen partial pressure of tumor tissues exhibit is significantly lower oxygen partial pressure compared to than that of normal tissues,. leading to The hypoxia inof the tumor microenvironment and resulting in leads to resistance to tumor treatments. Strategies to mitigate There are several methods to improve the hypoxia include enhancing of the tumor microenvironment, such as increasing blood flow perfusionblood perfusion and increasing oxygen supply, for example, by decomposing hydrogen peroxide within the tumor. Improving tumor hypoxiac in the tumor microenvironment could potentially may improve the efficacy ofbe a way to improve cancer treatments efficacy. Previous studies have demonstrated shown that ultrasound of appropriate intensity when ultrasound combined with microbubbles, can improve tumor blood flow perfusionblood perfusion; however,, but whether its effects on can improve tumor hypoxic tumor hypoxia microenvironment remainsis still unclear. This study aimeds to assess clarify the effects of low-frequency, non--focused ultrasound combined with microbubbles at different intensities on tumor microenvironment hypoxia and to identify screen the optimal ultrasound acoustic parameters for alleviating combination to improve tumor hypoxic tumor hypoxia microenvironment. Rabbits with VX2 tumors received were treated with ultrasound and combined with microbubbles treatments at different acoustic pressures and pulse repetition frequencies. The changes in tumor tissue hypoxia before and after treatment were observed by direct measuringement of tumor tissue oxygen partial pressure directly within tumor tissue and immunohistochemical staining for of hypoxia-inducible factor-1α (HIF-1α). RThe results indicated showed that low-frequency, non--focused ultrasound at 0.5 MPa/20 Hz and 0.5 MPa/40 Hz, when combined with microbubbles, couldcan increase tumor tissue blood flow perfusionblood perfusion and improve the tumor hypoxiac in tumor tissues microenvironment. This Our study provides a new method for improving hypoxia in the tumor microenvironment (TME)to improve tumor microenvironment hypoxia.