Antiapoptotic activity of autocrine interleukin-22 and therapeutic effects of interleukin-22-small interfering RNA on human lung cancer xenografts

Weici Zhang, Yongyan Chen, Haiming Wei, Chaogu Zheng, Rui Sun, Jian Zhang, Zhigang Tian

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

Purpose: Non-small cell lung carcinoma (NSCLC)is one of most common malignant diseases and usually is resistant against apoptosis-inducing chemotherapy. This study is to explore the antiapoptotic mechanisms of interleukin (IL)-22 in human lung cancer. Experimental Design: Nineteen cases with stage I to III NSCLC were collected to determine the expression of IL-22. Stable transfection of human IL-22 cDNA into A549 and PG cells and trans- fection of IL-22-RNA interference (RNAi)into these cancer cell lines were done to reveal the molecular mechanisms of IL-22. Results: It was found that IL-22 was highly expressed in primary tumor tissue, malignant pleural effusion, and serum of patients with NSCLC. IL-22R1 mRNA was also detected in lung cancer tissues as well as lung cancer cell lines. Overexpression of IL-22 protected lung cancer cell lines from serum starvation-induced and chemotherapeutic drug-induced apoptosis via activation of STAT3 and its downstream antiapoptotic proteins such as Bcl-2 and Bcl-xL and inactivation of extracellular signal-regulated kinase 1/2. Exposure to blocking antibodies against IL-22R1 or transfection with the IL-22-RNAi plasmid in vitro resulted in apoptosis of these lung cancer cells via STAT3 and extracellular signal-regulated kinase 1/2 pathways. Furthermore, an in vivo xenograft study showed that administration of IL-22-RNAi plasmids significantly inhibited the human tumor cell growth in BALB/c nude mice. Conclusions: Our study indicates that autocrine production of IL-22 contributes to human lung cancer cell survival and resistance to chemotherapy through the up-regulation of antiapoptotic proteins.

Original languageEnglish (US)
Pages (from-to)6432-6439
Number of pages8
JournalClinical Cancer Research
Volume14
Issue number20
DOIs
StatePublished - Oct 15 2008
Externally publishedYes

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Therapeutic Uses
Heterografts
Small Interfering RNA
Lung Neoplasms
RNA Interference
Non-Small Cell Lung Carcinoma
Transfection
Mitogen-Activated Protein Kinase 3
Interleukins
Mitogen-Activated Protein Kinase 1
Apoptosis
Cell Line
Plasmids
interleukin-22
Malignant Pleural Effusion
Drug Therapy
Neoplasms
Blocking Antibodies
Starvation
Serum

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Antiapoptotic activity of autocrine interleukin-22 and therapeutic effects of interleukin-22-small interfering RNA on human lung cancer xenografts. / Zhang, Weici; Chen, Yongyan; Wei, Haiming; Zheng, Chaogu; Sun, Rui; Zhang, Jian; Tian, Zhigang.

In: Clinical Cancer Research, Vol. 14, No. 20, 15.10.2008, p. 6432-6439.

Research output: Contribution to journalArticle

Zhang, Weici ; Chen, Yongyan ; Wei, Haiming ; Zheng, Chaogu ; Sun, Rui ; Zhang, Jian ; Tian, Zhigang. / Antiapoptotic activity of autocrine interleukin-22 and therapeutic effects of interleukin-22-small interfering RNA on human lung cancer xenografts. In: Clinical Cancer Research. 2008 ; Vol. 14, No. 20. pp. 6432-6439.
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