肺岩宁方对肺癌小鼠CD4+CD25+调节性T细胞比例及Foxp3表达的影响

doi:10.3736/jcim20120515

Abstract

Objective: To study the effects of Feiyanning Decoction, a compound traditional Chinese herbal medicine, on the ratio of CD4 ⁺CD25 ⁺ regulatory T cells and expression of transcription factor Foxp3 in mice with Lewis lung cancer.

Methods: Thirty-two male wild-type C57BL/6 mice aging from 6 to 8 weeks were inoculated with Lewis lung cancer cells to establish the tumor-bearing model of Lewis lung carcinoma and were randomly divided into model group, Chinese medicine group, chemotherapy group and Chinese medicine combined with chemotherapy group. After intervention for 14 d with corresponding drugs, behaviors, physical signs and changes of feed consumption of the mice were observed. All mice were sacrificed after drug treatment, and tumors and organs were removed to weigh and calculate organ indexes (lung index, spleen index and thymus index). The percentages of CD4 ⁺CD25 ⁺ regulatory T cells in the thymus, spleen and tumor were determined by flow cytometry. The expression of Foxp3 mRNA in the thymus, spleen and tumor tissues was detected by quantitative real-time polymerase chain reaction.

Results: Compared with those in the model group, the mice in the Chinese medicine group showed significant reductions in spleen and thymus indexes and tumor weight, and elevation in the body weight without tumor (P<0.05). The numbers of CD4 ⁺CD25 ⁺ regulatory T cells in spleen, thymus and tumor were lower in the Chinese medicine group than in the model group (P<0.05). The expression of Foxp3 mRNA in spleen, thymus and tumor was significantly down-regulated in the Chinese medicine group compared with the model group (P<0.05). There were no significant differences in CD4 ⁺CD25 ⁺ regulatory T cell ratio and Foxp3 mRNA expression between the Chinese medicine combined with chemotherapy group and the chemotherapy group.

Conclusion: Feiyanning Decoction can enhance the antitumor immune response and thus play a role in antitumor therapy by reducing the ratio of CD4 ⁺CD25 ⁺ regulatory T cells and down-regulating the expression of Foxp3 mRNA.

Key words: Lewis lung cancer, regulatory T cells, Foxp3, drugs, Chinese herbal, mice

Jing Guo, Ju-yong Wang, Zhan Zheng, Qing Wang, Chang-sheng Dong . Effects of Chinese herbal medicine Feiyanning Decoction on the ratio of CD4+CD25+ regulatory T cells and expression of transcription factor Foxp3 in mice bearing Lewis lung carcinoma. Journal of Chinese Integrative Medicine, 2012, 10(5): 584-590.

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URL: http://www.jcimjournal.com/EN/10.3736/jcim20120515

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Target gene	Forward primer and reverse primer	Fragment length (bp)	Annealing temperature (℃)	Cycle
Foxp3	F: 5′-TAGTTCCTTCCCAGAGTTCTTCC-3′	382	65.0	40
	R: 5′-AGATTTCATTGAGTGTCCTCTGC-3′
β-actin	F: 5′-CACCCGCGAGTACAACCTTC-3′	207	60.4	40
	R: 5′-CCCATACCCACCATCACACC-3′

Group	n	Consumption of food of each group (g)
Group	n	Day 0	Day 3	Day 7	Day 11	Day 15
Model	8	18.66	18.40	23.94	21.17	20.37
Chinese medicine	8	18.07	18.45	23.03	22.99	22.94
Chemotherapy	8	18.57	18.19	13.50	11.15	8.22
Combined treatment	8	18.55	18.35	15.82	13.18	13.13

Group	n	Body weight (g)
Group	n	Day 0	Day 3	Day 7	Day 11	Day 15
Model	8	18.62±0.65	19.09±0.66	19.99±0.71	20.42±0.77	20.45±0.70
Chinese medicine	8	18.55±0.80	19.12±0.90	19.74±0.83	20.23±0.82	20.71±0.80
Chemotherapy	8	18.42±0.54	18.01±0.49	16.81±0.38	15.99±0.33	15.39±0.50
Combined treatment	8	18.47±0.56	18.15±0.62	17.55±0.55^△	16.41±0.86	15.55±0.58

Group	n	Body weight (x±s, g)	Body weight without tumor (x±s, g)	Tumor weight (x±s, g)	Inhibition rate of tumor (%)
Model	8	20.45±0.70	16.29±0.79	4.16±0.33	—
Chinese medicine	8	20.71±0.80	17.42±0.82**	3.29±0.19**	20.91
Chemotherapy	8	15.39±0.50	13.43±0.58	1.95±0.34	53.13
Combined treatment	8	15.55±0.58	14.05±0.64^△△	1.51±0.20	63.70

Group	n	Index of organs (mg/g)
Group	n	Lung	Spleen	Thymus
Model	8	11.01±1.26	9.54±0.75	4.76±0.4
Chinese medicine	8	10.59±1.31	8.22±0.64^**	4.12±0.29^*
Chemotherapy	8	12.40±1.13	5.63±0.78	2.95±0.32
Combined treatment	8	11.54±1.32	6.31±0.34^△	3.36±0.26^△

Effects of Chinese herbal medicine Feiyanning Decoction on the ratio of CD4+CD25+ regulatory T cells and expression of transcription factor Foxp3 in mice bearing Lewis lung carcinoma

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