Effects of FA-PEG-hyd-DOX linker on the growth and cardiac toxicity of subcutaneous transplanted tumors of nude mice with liver cancer

doi:10.3877/cma.j.issn.2095-2015.2026.02.002

Abstract

Abstract:

Objective

To investigate the effects of the folate-polyethylene glycol-doxorubicin (FA-PEG-hyd-DOX) linker on the growth and cardiac toxicity of subcutaneous transplanted tumors of nude mice with liver cancer.

Methods

A total of 60 4-6 weeks nude mice were randomly divided into 5 groups, which were control group, DOX group, linker 1 group, linker 2 group and linker 3 group, with 12 mice in each group. The control group was injected with physiological saline solution, the DOX group was injected with DOX (dose 5.0 mg/kg), while the linker 1 group, linker 2 group and linker 3 group were injected with FA-PEG-hyd-DOX linker (dose 2.5, 5.0 and 10.0 mg/kg) was injected in groups 1, 2 and 3, respectively. The tumor volume and body mass were compared in nude mice at different time points, and the morphological changes of tumor tissue in nude mice after administration were compared. The relative expression levels of B-cell lymphoma-2 (Bcl-2), Bcl2-associated X (Bax)、myeloid cell leukemia-1 (Mcl-1), cleaved cysteine-dependent aspartate-specific protease-3 (cleaved caspase-3) and Ki-67 in nude mice after administration were compared. The distribution of DOX in the hearts, livers, and kidneys of nude mice and the hematological indexes were compared.

Results

After 20 days of administration, the tumor volume of control group, DOX group and linker 1 group were significantly higher than that of linker 2 group and linker 3 group (P<0.05). After 20 days of administration, the body weight of DOX group and linker 3 group was significantly lower than that of linker 2 group, linker 1 group and control group (P<0.05). The expressions of Bcl-2, Mcl-1 and Ki-67 in linker 2 and linker 3 groups were significantly lower than those in DOX group and linker 1 group, and the expressions of Bax and cleaved caspase-3 were significantly higher than those in control group and linker 1 group (P<0.05). Compared with the DOX group, the distribution of DOX in the heart was reduced in the linker 2 group. The levels of CK in linker 1 group, linker 2 group and linker 3 group were significantly lower than those in DOX group (P<0.05).

Conclusion

Compared with DOX, the FA-PEG-hyd-DOX linker can effectively inhibit the volume of subcutaneous transplanted tumors in nude mice with liver cancer, having good anti-tumor effects, and can more effectively promote tumor cell apoptosis, reducing damage to the heart.

Key words: Liver cancer, Folate-polyethylene glycol-doxorubicin linker, Subcutaneous transplanted tumors, Nude mice, Apoptosis

Bo Li, Weiliang Ye, Jingwen Zhang, Wenwen Shang. Effects of FA-PEG-hyd-DOX linker on the growth and cardiac toxicity of subcutaneous transplanted tumors of nude mice with liver cancer[J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2026, 16(02): 101-107.

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Figures/Tables 7

References 23

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组别	例数	Bcl-2	Bax	Mcl-1	Ki-67	cleaved-caspase-3
对照组	12	1.24±0.11	0.30±0.03	0.60±0.02	0.88±0.06	0.79±0.02
DOX组	12	0.80±0.07^a	0.71±0.02^a	0.41±0.03^a	0.67±0.05^a	0.98±0.02^a
连接物1组	12	0.97±0.06^ab	0.56±0.02^ab	0.52±0.01^ab	0.71±0.04^ab	0.87±0.04^ab
连接物2组	12	0.41±0.04^abc	1.34±0.05^abc	0.30±0.05^abc	0.57±0.05^abc	1.13±0.05^abc
连接物3组	12	0.37±0.03^abc	1.37±0.06^abc	0.27±0.03^abc	0.53±0.06^abc	1.16±0.02^abc
F		349.076	2570.576	460.211	98.697	628.356
P		<0.001	<0.001	<0.001	<0.001	<0.001

组别	例数	Bcl-2	Bax	Mcl-1	Ki-67	cleaved-caspase-3
对照组	12	1.24±0.11	0.30±0.03	0.60±0.02	0.88±0.06	0.79±0.02
DOX组	12	0.80±0.07^a	0.71±0.02^a	0.41±0.03^a	0.67±0.05^a	0.98±0.02^a
连接物1组	12	0.97±0.06^ab	0.56±0.02^ab	0.52±0.01^ab	0.71±0.04^ab	0.87±0.04^ab
连接物2组	12	0.41±0.04^abc	1.34±0.05^abc	0.30±0.05^abc	0.57±0.05^abc	1.13±0.05^abc
连接物3组	12	0.37±0.03^abc	1.37±0.06^abc	0.27±0.03^abc	0.53±0.06^abc	1.16±0.02^abc
F		349.076	2570.576	460.211	98.697	628.356
P		<0.001	<0.001	<0.001	<0.001	<0.001

组别	鼠数	谷丙转氨酶(U/L)	谷草转氨酶(U/L)	肌酐(μmol/L)	尿素氮(mmol/L)	肌酸激酶(IU/L)
对照组	12	44.61±1.73	120.03±4.97	17.48±2.21	7.86±2.48	70.37±16.15
DOX组	12	52.06±6.02^a	135.58±16.47^a	24.96±6.03^a	13.12±3.98^a	178.32±37.11^a
连接物1组	12	49.21±2.46^a	132.87±7.48^a	22.69±1.60^a	11.41±2.38^a	90.51±15.51^ab
连接物2组	12	49.79±4.20^a	133.40±6.85^a	23.52±2.49^a	11.95±1.48^a	91.21±14.02^ab
连接物3组	12	50.63±3.72^a	134.65±5.94^a	24.42±2.20^a	12.42±2.00^a	92.75±12.17^ab
F		4.577	3.397	9.822	7.496	48.071
P		0.003	0.012	<0.001	<0.001	<0.001

组别	鼠数	谷丙转氨酶(U/L)	谷草转氨酶(U/L)	肌酐(μmol/L)	尿素氮(mmol/L)	肌酸激酶(IU/L)
对照组	12	44.61±1.73	120.03±4.97	17.48±2.21	7.86±2.48	70.37±16.15
DOX组	12	52.06±6.02^a	135.58±16.47^a	24.96±6.03^a	13.12±3.98^a	178.32±37.11^a
连接物1组	12	49.21±2.46^a	132.87±7.48^a	22.69±1.60^a	11.41±2.38^a	90.51±15.51^ab
连接物2组	12	49.79±4.20^a	133.40±6.85^a	23.52±2.49^a	11.95±1.48^a	91.21±14.02^ab
连接物3组	12	50.63±3.72^a	134.65±5.94^a	24.42±2.20^a	12.42±2.00^a	92.75±12.17^ab
F		4.577	3.397	9.822	7.496	48.071
P		0.003	0.012	<0.001	<0.001	<0.001

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