Efficacy of rapamycin arterial perfusion combined with 131I-FAP loaded dextran microspheres for interventional embolization in the treatment of rabbits with liver transplantation tumor

doi:10.3760/cma.j.cn371439-20241009-00060

Abstract

Abstract:

Objective To investigate the efficacy of rapamycin arterial perfusion combined with ¹³¹I-fibroblast activation protein （FAP） loaded dextran microspheres in the treatment of rabbits with liver transplantation tumor. Methods Fifty male New Zealand white rabbits were selected. Forty white rabbits were used to establish liver transplantation tumor models and were randomly divided into a negative control （based on arterial perfusion with the same volume of normal saline， MO） group， rapamycin arterial perfusion （RA） group， ¹³¹I-FAP loaded dextran microspheres for interventional embolization therapy （IF） group， and rapamycin arterial perfusion combined with ¹³¹I-FAP-loaded dextran microspheres interventional embolization therapy （RI） group by the random number table method， with 10 rabbits in each group. The remaining 10 unmodeled white rabbits were classified as the normal （based on arterial perfusion with the same volume of normal saline， NO） group. The pathological morphology of tumor tissues was detected by HE staining， liver function was detected by automatic biochemical analyzer， apoptosis of tumor cells was detected by TUNEL method， and the protein expression of vascular endothelial growth factor （VEGF） and vascular endothelial growth factor receptor （VEGFR） in liver tissues was detected by Western blotting. Results The tumor mass of MO group， RA group， IF group and RI group was （20.33±2.39），（14.62±1.23），（14.34±1.22），（8.28±0.84） g， respectively. Tumor volumes were （0.87±0.13），（0.51±0.09），（0.53±0.08），（0.32±0.02） cm³， respectively. Tumor necrosis rates were （21.11±2.14）%，（32.18±3.25）%，（32.29±3.28）%，（48.53±4.37）%， respectively. Tumor suppression rates were （0.00±0.00）%，（24.66±2.47）%，（24.13±2.46）%，（45.55±4.51）%， respectively. There were statistically significant differences （F=316.40， P<0.001； F=159.50， P<0.001； F=356.10， P<0.001； F=571.30， P<0.001）； there were statistically significant differences in RA， IF and RI groups compared with the MO group （all P<0.05）； there were statistically significant differences between RI group and IF group （all P<0.05）. Tumor cells of MO group showed infiltrating growth， with more mitotic images， no obvious necrosis， and a large number of inflammatory cell infiltration. Cancer nests in RA group， IF group and RI group became significantly smaller， tumor cells showed swelling， nuclear contraction and a large number of necrosis， and inflammatory cell infiltration was significantly reduced， among which the improvement was most obvious in RI group. The albumin （ALB） level of NO group， MO group， RA group， IF group and RI group was （40.55±4.38），（17.34±1.02），（22.65±2.18），（22.37±2.17），（29.01±2.83） g/L， respectively. The alanine aminotransferase （ALT） level was （19.68±1.34），（92.17±9.24），（78.71±7.39），（78.35±7.40），（50.30±5.12） U/L， respectively. The aspartate aminotransferase （AST） level was （74.27±7.48），（182.21±20.23），（165.78±16.05），（165.26±16.09），（102.33±11.11） U/L， respectively. The total bilirubin （TBIL） level was （22.42±2.58），（82.24±8.35），（61.86±6.17），（61.53±6.16），（46.45±4.53） μmoL/L， respectively. There were statistically significant differences （F=105.90， P<0.001； F=189.00， P<0.001； F=99.57， P<0.001； F=142.10， P<0.001）； there were statistically significant differences in MO， RA， IF， RI groups compared with the NO group （all P<0.05）； there were statistically significant differences in RA， IF， RI groups compared with the MO group （all P<0.05）； there were statistically significant differences between IF group and RI group （all P<0.05）. The apoptosis rates in MO group， RA group， IF group and RI group were （9.01±1.23）%，（15.65±1.68）%，（15.72±1.69）% and （24.34±2.12）%， respectively， and there was a statistically significant difference （F=135.30， P<0.001）； there were statistically significant differences in RA， IF and RI groups compared with the MO group （all P<0.05）； there was a statistically significant difference between RI group and IF group （P<0.05）. VEGF expression level in NO group， MO group， RA group， IF group and RI group was 1.33±0.13， 2.28±0.21， 1.88±0.19， 1.86±0.18 and 1.50±0.14， respectively. VEGFR expression level was 1.32±0.09， 2.14±0.28， 1.91±0.18， 1.89±0.17， 1.62±0.15， respectively. There were statistically significant differences （F=45.84， P<0.001； F=29.05， P<0.001）； there were statistically significant differences in MO， RA， IF， RI groups compared with the NO group （all P<0.05）； there were statistically significant differences in RA， IF， RI groups compared with the MO group （all P<0.05）； there were statistically significant differences between IF group and RI group （both P<0.05）. Conclusions Rapamycin arterial perfusion combined with ¹³¹I-FAP-loaded dextran microspheres interventional embolization therapy in the treatment of rabbits with liver transplantation tumor can effectively inhibit tumor growth， enhance the tumor necrosis rate， tumor inhibition rate and apoptotic ability， improve liver function indicators， and has a significant therapeutic effect on rabbits with liver transplantation tumor.

Key words: Liver neoplasms, Rabbits, Sirolimus, Embolization， therapeutic

Hao Chunhai. Efficacy of rapamycin arterial perfusion combined with ¹³¹I-FAP loaded dextran microspheres for interventional embolization in the treatment of rabbits with liver transplantation tumor[J]. Journal of International Oncology, 2025, 52(6): 353-359.

Figures/Tables 5

References 20

[1]	Li F, Liu P, Mi W, et al. Blocking methionine catabolism induces senescence and confers vulnerability to GSK3 inhibition in liver cancer[J]. Nat Cancer, 2024, 5(1): 131-146. DOI: 10.1038/s43018-023-00671-3.
[2]	Lv H, Zong Q, Chen C, et al. TET2-mediated tumor cGAS triggers endothelial sting activation to regulate vasculature remodeling and anti-tumor immunity in liver cancer[J]. Nat Commun, 2024, 15(1): 6. DOI: 10.1038/s41467-023-43743-9.
[3]	Yang H, Cheng J, Zhuang H, et al. Pharmacogenomic profiling of intra-tumor heterogeneity using a large organoid biobank of liver cancer[J]. Cancer Cell, 2024, 42(4): 535-551.e8. DOI: 10.1016/j.ccell.2024.03.004. pmid: 38593780
[4]	Xue Y, Ruan Y, Wang Y, et al. Signaling pathways in liver cancer: pathogenesis and targeted therapy[J]. Mol Biomed, 2024, 5(1): 20. DOI: 10.1186/s43556-024-00184-0.
[5]	Zhang Z, Shen C, Zhou F. Correction to: the natural medicinal fungus huaier promotes the anti-hepatoma efficacy of sorafenib through the mammalian target of rapamycin-mediated autophagic cell death[J]. Med Oncol, 2023, 40(2): 83. DOI: 10.1007/s12032-022-01920-8.
[6]	朱鸷翔, 沈松鹤, 赵森, 等. 腹主动脉灌注雷帕霉素联合肝动脉化疗治疗肝移植瘤兔模型疗效分析[J]. 现代肿瘤医学, 2020, 28(23): 4032-4036. DOI: 10.3969/j.issn.1672-4992.2020.23.003.
[7]	Wu X, Ge L, Shen G, et al. ¹³¹I-labeled silk fibroin microspheres for radioembolic therapy of rat hepatocellular carcinoma[J]. ACS Appl Mater Interfaces, 2022, 14(19): 21848-21859. DOI: 10.1021/acsami.2c00211.
[8]	Liu X, Li D, Ma T, et al. Autophagy inhibition improves the targeted radionuclide therapy efficacy of ¹³¹I-FAP-2286 in pancreatic cancer xenografts[J]. J Transl Med, 2024, 22(1): 156. DOI: 10.1186/s12967-024-04958-6.
[9]	谷铁树, 李博, 吴勇超, 等. 碘油与葡聚糖微球栓塞兔肝VX2移植瘤疗效对比[J]. 河北医科大学学报, 2020, 41(9): 1089-1093. DOI: 10.3969/j.issn.1007-3205.2020.09.022.
[10]	Prasad YR, Anakha J, Pande AH. Treating liver cancer through arginine depletion[J]. Drug Discov Today, 2024, 29(4): 103940. DOI: 10.1016/j.drudis.2024.103940.
[11]	Tong Y, Wang F, Li S, et al. Histone methyltransferase KMT5C drives liver cancer progression and directs therapeutic response to PARP inhibitors[J]. Hepatology, 2024, 80(1): 38-54. DOI: 10.1097/HEP.0000000000000559.
[12]	Wang Y, Lin W, Huang G, et al. The therapeutic principle of combined clearing heat and resolving toxin plus TACE on primary liver cancer: a systematic review and meta-analysis[J]. J Ethnopharmacol, 2024, 319(Pt 1): 117072. DOI: 10.1016/j.jep.2023.117072.
[13]	Ma H, Li F, Shen G, et al. Synthesis and preliminary evaluation of ¹³¹I-labeled FAPI tracers for cancer theranostics[J]. Mol Pharm, 2021, 18(11): 4179-4187. DOI: 10.1021/acs.molpharmaceut.1c00566.
[14]	Ardjmand D, Kubota Y, Sato M, et al. Selective synergy of rapamycin combined with methioninase on cancer cells compared to normal cells[J]. Anticancer Res, 2024, 44(3): 929-933. DOI: 10.21873/anticanres.16887. pmid: 38423628
[15]	童倩倩. 负载-(131)I-FAP的葡聚糖微球的构建并用于兔VX2肝移植瘤介入栓塞治疗的初步研究[D]. 宜春: 宜春学院, 2023. DOI: 10.27928/d.cnki.gycxy.2023.000014.
[16]	Chen M, Liu W, Liu B. Cryoablation with KCl solution enhances necrosis and apoptosis of HepG2 liver cancer cells[J]. Ann Biomed Eng, 2024, 52(8): 2118-2133. DOI: 10.1007/s10439-024-03512-1. pmid: 38615077
[17]	Shi Z, Hu M, Bian J. 99mTc-HYNIC-annexin V detection of apoptosis in the rabbit model of liver cancer[J]. Cell Mol Biol (Noisy-le-grand), 2024, 70(7): 143-147. DOI: 10.14715/cmb/2024.70.7.20. pmid: 39097883
[18]	孙潺, 张轩斌, 赵江, 等. 雷帕霉素对肺癌SPC-A-1细胞增殖和凋亡的影响[J]. 临床肺科杂志, 2023, 28(6): 829-833. DOI: 10.3969/j.issn.1009-6663.2023.06.004.
[19]	Wu T, Yao Y, Sun R, et al. Arterial instillation of rapamycin in treatment of rabbit hepatic xenograft tumors and its effects on VEGF, iNOS, HIF-1α, Bcl-2, Bax expression and microvessel density[J]. Sci Prog, 2021, 104(3): 368504211026417. DOI: 10.1177/00368504211026417.
[20]	You M, Fu J, Lv X, et al. Saikosaponin b2 inhibits tumor angioge-nesis in liver cancer via down-regulation of VEGF/ERK/HIF-1α signaling[J]. Oncol Rep, 2023, 50(1): 136. DOI: 10.3892/or.2023.8573.

组别	肿瘤质量（g）	肿瘤体积（cm³）	肿瘤坏死率（%）	抑瘤率（%）
MO组	20.33±2.39	0.87±0.13	21.11±2.14	0.00±0.00
RA组	14.62±1.23^a	0.51±0.09^a	32.18±3.25^a	24.66±2.47^a
IF组	14.34±1.22^a	0.53±0.08^a	32.29±3.28^a	24.13±2.46^a
RI组	8.28±0.84^abc	0.32±0.02^abc	48.53±4.37^abc	45.55±4.51^abc
F值	316.40	159.50	356.10	571.30
P值	<0.001	<0.001	<0.001	<0.001

组别	ALB（g/L）	ALT（U/L）	AST（U/L）	TBIL（μmoL/L）
NO组	40.55±4.38	19.68±1.34	74.27±7.48	22.42±2.58
MO组	17.34±1.02^a	92.17±9.24^a	182.21±20.23^a	82.24±8.35^a
RA组	22.65±2.18^ab	78.71±7.39^ab	165.78±16.05^ab	61.86±6.17^ab
IF组	22.37±2.17^ab	78.35±7.40^ab	165.26±16.09^ab	61.53±6.16^ab
RI组	29.01±2.83^abcd	50.30±5.12^abcd	102.33±11.11^abcd	46.45±4.53^abcd
F值	105.90	189.00	99.57	142.10
P值	<0.001	<0.001	<0.001	<0.001

Efficacy of rapamycin arterial perfusion combined with ¹³¹I-FAP loaded dextran microspheres for interventional embolization in the treatment of rabbits with liver transplantation tumor

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