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Wenxia Changfu Formula (温下肠腑方) induces apoptosis of lung adenocarcinoma in a transplanted tumor model of drug-resistance nude mice

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Abstract

Objective

To explore the apoptosis mechanism of Wenxia Changfu Formula (温下肠腑方, WCF) in reversing drug resistance of lung cancer in vivo.

Methods

Thirty model mice were randomly assigned to three groups: control group, cisplatin (CDDP) group, and WCF group. A transplanted tumor model of lung adenocarcinoma was established in all groups. Mice in the WCF group received intragastric administration of WCF (0.2 mL/10 g body weight) everyday in addition to CDDP intraperitoneally (5 mg/kg body weight) twice a week. The mice in the CDDP group received CDDP intraperitoneally (5 mg/kg body weight) twice a week, while the control group received normal saline intraperitoneally (0.2 mL/10 g body weight) everyday. The weight of the nude mice and respective tumors, tumor volume and tumor-inhibiting rate were measured. Electron microscopy was used to observe the existence of apoptosis body. Apoptosis index (AI) was detected by TdT-mediated dUTP nick end labeling staining. The expression of Fas and FasL mRNA was investigated by reverse transcription polymerase chain reaction, while immunohistochemistry was applied to detect the protein expression of Fas and FasL, caspase-3 and caspase-activated DNase (CAD), respectively.

Results

Compared with CDDP group and control group, WCF could significantly reduce the tumor volume from the 19th day and alleviate the tumor weight (P <0.05), and the apoptosis body was found in tumor cells in the WCF group. WCF could also enhance the level of AI, up-regulate the expression of caspase apoptosis pathway related protein caspase-3 and CAD, as well as the expression of Fas, FasL mRNA and protein (P <0.05).

Conclusion

WCF could improve the sensitivity of tumor cells to CDDP and reverse the drug resistance by inducing the apoptosis.

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Authors and Affiliations

  1. School of Basic Medical Science, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China

    Xu-ming Ji  (季旭明), Zhi-chun Wu  (吴智春), Guo-wei Liu  (刘国伟), Hua-yun Yu  (于华芸) & Bing Ouyang  (欧阳兵)

  2. Department of Neurology, Qilu Hospital, Shandong University, Jinan, 250012, China

    Heng Liu  (刘 恒)

  3. Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

    Zheng-tao Wang  (王峥涛) & Xiao-hui Wei  (尉小慧)

Authors
  1. Xu-ming Ji  (季旭明)
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  2. Zhi-chun Wu  (吴智春)
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  3. Guo-wei Liu  (刘国伟)
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  4. Hua-yun Yu  (于华芸)
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  5. Heng Liu  (刘 恒)
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  6. Zheng-tao Wang  (王峥涛)
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  7. Xiao-hui Wei  (尉小慧)
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  8. Bing Ouyang  (欧阳兵)
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Corresponding author

Correspondence to Zhi-chun Wu  (吴智春).

Additional information

Supported by the National Natural Science Foundation of China (No. 81072832, 81273634), and the Opening Project of Shanghai Key Laboratory of Complex Prescription (No. 11DZ2272300), National Science and Technology Major Projects for "Major New Drugs Innovation and Development (No. 2010Z0940)

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Ji, Xm., Wu, Zc., Liu, Gw. et al. Wenxia Changfu Formula (温下肠腑方) induces apoptosis of lung adenocarcinoma in a transplanted tumor model of drug-resistance nude mice. Chin. J. Integr. Med. 22, 752–758 (2016). https://doi.org/10.1007/s11655-015-2087-4

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  • DOI: https://doi.org/10.1007/s11655-015-2087-4

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