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Journal of Chinese Integrative Medicine ›› 2008, Vol. 6 ›› Issue (6): 616-620.doi: 10.3736/jcim20080614

• Original Experimental Research • Previous Articles     Next Articles

Feiyanning Decoction down-regulates the expressions of phosphorylated Akt and hypoxia inducible factor-1α proteins in transplanted lung adenocarcinoma in nude mice

Ming Zhang1,2(), Zhen-ye Xu1,2, Bing Bai1,2, Yun Dong3   

  1. 1. Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
    2. Cancer Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
    3. Department of Integrated Traditional Chinese and Western Medicine,Shanghai Chest Hospital, Shanghai Jiao tong University, Shanghai 200030, China
  • Received:2007-11-26 Online:2008-06-20 Published:2008-06-15
  • Contact: ZHANG Ming E-mail:gason2000@126.com

Objective: To observe the effects of Feiyanning Decoction, a compound traditional Chinese herbal medicine, in inhibiting the growth of transplanted A549 tumors in nude mice and the expressions of p-Akt and HIF-1α in A549 tumors.
Methods: Thirty-two nude mice were transplanted with human lung adenocarcinoma cells (A549 cells) to make the mice model, and then randomly divided into four groups: untreated group (n=8), diamminedichloroplatinum (DDP) group (n=8), Feiyanning group (n=8) and DDP plus Feiyanning group (n=8). The nude mice in DDP group and DDP plus Feiyanning group were treated with DDP 0.1 mg by peritoneal injection on the 1st, 3rd and 5th day after model establishment. The nude mice in the Feiyanning group and the DDP plus Feiyanning group were treated with Feiyanning Decoction for 21 days. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression of HIF-1α mRNA in tumors, and immunohistochemical method was used to detect the expressions of p-Akt and HIF-1α proteins in tumors.
Results: The inhibition rates of tumor in Feiyanning group and DDP plus Feiyanning group were 34.17% and 64.38% respectively. RT-PCR showed that the expression level of HIF-1α mRNA in DDP plus Feiyanning group was lower than that in the untreated group (P<0.05). Immunohistochemical staining showed that the optical density (OD) indexes of HIF-1α in DDP group, Feiyanning group and DDP plus Feiyanning group were lower than that in the untreated group (P<0.01). The expressions of p-Akt in the Feiyanning group and DDP plus Feiyanning group were lower than that in the untreated group either (P<0.05).
Conclusion: Feiyanning Decoction is effective in inhibiting the growth of lung cancer. And the effect of inhibiting the expression of HIF-1α protein by Feiyanning Decoction may correlate with down-regulation of p-Akt.

Key words: reinforcing qi and nourishing jing, Feiyanning Decoction, human lung adenocarcinoma cell strain, hypoxia inducible factor 1, alpha subunit, Akt, nude mice

CLC Number: 

  • R734.2

Table 1

Tumor weights and inhibition rates of tumor in nude mice in different groups"

Group n Tumor weight ($\bar{x}$±s, g) Inhibition rate of tumor (%)
Untreated 8 0.60±0.21
DDP 8 0.27±0.20** 55.83
Feiyanning 8 0.40±0.16* 34.17
DDP plus Feiyanning 8 0.21±0.14** 64.38

Table 2

Ratio of HIF-1α mRNA/GAPDH in tumor tissues of nude mice in different groups"

Group n Ratio of HIF-1α mRNA/GAPDH
Untreated 8 0.905 4
DDP 8 0.772 0
Feiyanning 8 0.809 2
DDP plus Feiyanning 8 0.656 1*

Figure 1

Expression of HIF-1α mRNA in tumor tissues of nude mice in different groups A: Untreated group; B: DDP group; C: Feiyanning group; D: DDP plus Feiyanning group"

Table 3

Expressions of HIF-1α and p-Akt proteins in tumor tissues of nude mice in different groups ($\bar{x}$±s, ×10-3)"

Group n HIF-1α protein p-Akt protein
Untreated 8 66.32±15.5 19.22±4.67
DDP 8 5.63±1.32** 17.17±4.45
Feiyanning 8 10.23±4.41** 14.00±4.55*
DDP plus Feiyanning 8 4.84±1.96** 13.32±4.03*

Figure 2

Expressions of HIF-1α protein in tumor tissues of nude mice in different groups (Immunohistochemical staining, ×200) A: Untreated group; B: DDP group; C: Feiyanning group; D: DDP plus Feiyanning group."

Figure 3

Expressions of p-Akt protein in tumor tissues of nude mice in different groups (Immunohistochemical staining, ×200) A: Untreated group; B: DDP group; C: Feiyanning group; D: DDP plus Feiyanning group."

[1] Vaupel P.The role of hypoxia-induced factors in tumor progression[J].Oncologist, 2004,9 Suppl 5: 10-17
doi: 10.1634/theoncologist.9-90005-10 pmid: 15591418
[2] Birner P, Schindl M, Obermair A , et al. Expression of hypoxia-inducible factor 1 alpha in epithelial ovarian tumors: its impact on prognosis and on response to chemotherapy[J]. Clin Cancer Res, 2001,7(6):1661-1668
[3] Zhong H, De Marzo AM, Laughner E , et al. Overexpression of hypoxia-inducible factor 1 alpha in common human cancers and their metastases[J]. Cancer Res, 1999,59(22):5830-5835
[4] Blancher C, Moore JW, Robertson N , et al. Effects of ras and von Hippel-Lindau(VHL) gene mutations on hypoxia-inducible factor(HIF)-1 alpha, HIF-2 alpha, and vascular endothelial growth factor expression and their regulation by the phosphatidylinositol 3'-kinase/Akt signaling pathway[J]. Cancer Res, 2001,61(19):7349-7355
[5] Kakinuma Y, Ando M, Kuwabara M , et al. Acetylcholine from vagal stimulation protects cardiomyocytes against ischemia and hypoxia involving additive non-hypoxic induction of HIF-1alpha[J]. FEBS Lett, 2005,579(10):2111-2118
doi: 10.1016/j.febslet.2005.02.065
[6] Wang ZQ, Xu ZY . Exploration of "Qi-Benefiting and Essence-Nourishing Method" in the treatment of pulmonary cancer in middle and late stage[J]. Shanghai Zhong Yi Yao Da Xue Xue Bao, 2002,16(4):30-31
王中奇, 徐振晔 . 益气养精法治疗中晚期肺癌的探讨[J]. 上海中医药大学学报, 2002,16(4):30-31
[7] Xu ZY, Wang ZQ, Zhu YW , et al. Influence of "Feiyanning Decoction" on late non-small cell lung cancer metastasis and serum vascular endothelial growth factor[J]. Shanghai Zhong Yi Yao Da Xue Xue Bao, 2003,17(3):18-22
doi: 10.3969/j.issn.1008-861X.2003.03.006
徐振晔, 王中奇, 朱晏伟 , 等. 肺岩宁方对晚期非小细胞肺癌生长转移和血清VEGF的影响[J]. 上海中医药大学学报, 2003,17(3):18-22
doi: 10.3969/j.issn.1008-861X.2003.03.006
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