Image-Guided Radiofrequency Hyperthermia (RFH)-Enhanced Direct Chemotherapy of Hepatic Tumors: The Underlying Biomolecular Mechanisms.
Image-Guided Radiofrequency Hyperthermia (RFH)-Enhanced Direct Chemotherapy of Hepatic Tumors: The Underlying Biomolecular Mechanisms.
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DOI：
10.3389/fonc.2020.610543
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发表时间：
2020
影响因子：
4.7
通讯作者：
Yang X
中科院分区：
文献类型：
--
作者：
Qian K;Chen M;Zhang F;Chick JFB;Ji H;Zheng C;Yang X
评价射频热疗（RFH）联合瘤内化疗对兔VX2肝肿瘤的治疗效果，探讨局部热疗增强化疗的机制。将VX2细胞系和具有肝VX2肿瘤的兔随机分配到四个治疗组，包括：（1）多柔比星（DOX）加热疗/RFH的组合疗法（n = 6）;（2）仅DOX;（3）仅热疗/RFH（n = 6）;和（4）磷酸盐缓冲盐水处理的对照（n = 6）。治疗后24 h，使用流式细胞术和荧光显微镜检测细胞活力和VX 2肿瘤细胞对阿霉素的摄取。Western blot检测热休克蛋白70（HSP70）在肿瘤细胞和组织中的表达水平。对于收获的VX2肿瘤，使用荧光显微镜来评估阿霉素在肿瘤组织中的分布和渗透，并通过Western blot和免疫组织化学分析HSP70表达。RFH增强了阿霉素在VX 2细胞和兔肝VX 2肿瘤中的化疗效果，导致更高的凋亡和更低的细胞活力。流式细胞仪检测VX 2细胞凋亡情况，高温联合阿霉素组细胞凋亡率高于其他三组体外实验（分别为45.80 ± 1.27%、20.66 ± 0.71%、15.16 ± 0.81%和0.62 ± 0.06%，p <0.01）。Western blot和免疫组化定量分析显示，两种VX2肿瘤细胞中HSP70的表达均增加（1.28 ± 0.13vs 0.64 ± 0.13vs 0.83 ± 0.10vs 0.15 ± 0.03，p <0.05）（1.47 ± 0.13 vs 0.51 ± 0.13 vs 0.74 ± 0.11 vs 0.16 ± 0.04，p <0.01）。荧光显微镜显示联合治疗组肿瘤细胞中DOX的摄取增加。RFH/热疗通过促进肿瘤对DOX的摄取和HSP 70的表达，增强DOX对VX2肿瘤的化疗效果。
To evaluate the treatment effect of radiofrequency-induced hyperthermia (RFH) combined with intra-tumoral chemotherapy for rabbit VX2 liver tumors and explore the underlying mechanism that drives local hyperthermia-enhanced chemotherapy. VX2 cell lines and rabbits with liver VX2 tumors were randomly allocated to four treatment groups including: (1) combination therapy of Doxorubicin (DOX) plus hyperthermia/RFH (n=6); (2) DOX only; (3) hyperthermia/RFH only (n=6); and (4) phosphate-buffered saline-treated control (n=6). Cell viability and doxorubicin uptake by VX2 tumor cells were assayed using flow cytometry and fluorescence microscopy 24 h after treatments. Western blot was used to evaluate the expression level of heat shock protein 70 (HSP70) in tumor cells and tissues. For the harvested VX2 tumors, fluorescence microscopy was used to evaluate the distribution and penetration of doxorubicin in tumor tissues and HSP70 expression was analyzed by Western blot and immunohistochemistry. RFH enhanced the chemotherapeutic effect of doxorubicin in VX2 cells and rabbit liver VX2 tumors resulting in higher apoptosis and lower cell viability. Flowcytometry of VX2 cells showed more apoptotic cells in combination therapy of hyperthermia and DOX, compared with other three groups in-vitro experiments (45.80 ± 1.27% vs 20.66 ± 0.71%, vs 15.16 ± 0.81% and 0.62 ± 0.06%, respectively, p<0.01). The quantitative analysis by Western blot and immunohistochemistry showed increased expression of HSP70 in both VX2 tumor cells (1.28 ± 0.13 vs 0.64 ± 0.13 vs 0.83 ± 0.10 vs 0.15 ± 0.03, respectively, p<0.05) and tumors (1.47 ± 0.13 vs 0.51 ± 0.13 vs 0.74 ± 0.11 vs 0.16 ± 0.04, respectively, p <0.01). Fluorescence microscopy showed increased uptake of DOX in tumor cells in the combination therapy group. RFH/hyperthermia enhanced the chemotherapeutic effect of DOX in VX2 tumors by promoting the uptake of DOX and the expression HSP70 in tumors.
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