低频超声辐照微泡（USMB）通过破坏肿瘤微血管或血管内血栓形成等阻断肿瘤血供，其可以作为“栓塞剂”，类似经动脉化疗栓塞（TACE），不仅阻断肿瘤血供，同时使化疗药选择性地保留在靶组织。但是，我们的预实验结果揭示若USMB只能暂时阻断肿瘤血供，反而可能促进肿瘤组织的增长。为此，我们提出假说：USMB所致的暂时性肿瘤血流阻断，可能通过上调瘤体缺氧诱导因子-1α（HIF-1α）的表达，增强其缺氧耐受性，从而促进肿瘤生长。为了验证这一假说，我们将通过裸鼠前列腺癌移植瘤模型,测量USMB介导的化疗栓塞治疗后瘤体的大小，检测HIF-1α的表达，并采用RNA干扰作为抑制HIF-1α的手段，研究其对USMB介导的化疗栓塞后移植瘤生长、血管生成的影响。本研究将从抑制USMB化疗栓塞后缺氧应答这个新视点，为开展USMB化疗栓塞与抑制缺氧应答的联合疗法提供理论及实验基础。

Low-frequency ultrasound combing microbubbles (USMB) could disrupt tumor blood flowing by destroying tumor vasculature and intravasculature thrombosis. Therefore, USMB could be used as "embolic agent" to combing chemotherapy drugs to achieve chemoembolization,as it could not only obstruct the tumor blood supply, but also hold the drugs in tumor issues. Conceptually, this is a strategy similar to transarterial chemoembolization (TACE). However, our pre-experiment found that, if USMB can only block the blood temorarily, it induce tumor cells to grow more rapidly. So, we propose a hypothesis that, USMB may up-regulate the expression of hopoxia-inducible factor-1α (HIF-1α) in residual tumor cells, increase the ability of hypoxia-endurance, thus induce the residual tumor cells to grow more rapidly. In order to test this hypothesis, we will establish the prostate cancer xenograft in nude mice, measure the size of tumors and test the expression of HIF-1α after the treatment of USMB combing docetaxel, then use RNA interference to inhibite HIF-1α in tumors, and research the growth of xenografts and tumor angiogenesis after USMB. From a new perspective of inhibiting HIF-1α in tumors induced by USMB, this research will provide the theretical and practice basis for the combination of hypoxia-response inhibition and USMB mediated chemoembolization. We believe this research is of great significance for USMB mediated chemoembolization to clinical applications.

低频超声辐照微泡（USMB）通过破坏肿瘤微血管或血管内血栓形成等阻断肿瘤血供，其可以作为“栓塞剂”，类似经动脉化疗栓塞（TACE），不仅阻断肿瘤血供，同时使化疗药选择性地保留在靶组织。但是，USMB术后残存的瘤细胞的缺氧诱导因子-1α（HIF-1α）和血管内皮生长因子A（VEGFA）表达上调，增加了残余瘤灶的微血管密度，从而促进残余瘤灶的生长。我们构建了针对人前列腺癌PC3细胞HIF-1α的RNA干扰表达载体；体外细胞实验证实了载HIF-1α-shRNA超声微泡能够增强多西紫杉醇治疗前列腺癌PC-3细胞的化疗敏感性；体内实验明确了超声辐照载HIF-1α-shRNA微泡能够增强多西紫杉醇对裸鼠皮下PC3移植瘤的化疗栓塞治疗的疗效，并证实了这是通过降低超声微泡介导的化疗栓塞术后的缺氧应答和促进残余瘤灶的凋亡来实现的。本研究从抑制USMB化疗栓塞后缺氧应答这个新视点，为开展USMB化疗栓塞与抑制缺氧应答的联合疗法提供了理论及实验基础。