Antitumor activity and immunomodulatory effects of the intraperitoneal administration of Kanglaite in vivo in Lewis lung carcinoma

J Ethnopharmacol. 2012 Sep 28;143(2):680-5. doi: 10.1016/j.jep.2012.07.025. Epub 2012 Jul 31.

Abstract

Aims of the study: Kanglaite (KLT) is a useful antitumor drug with proven effects when combined with chemotherapy, radiotherapy or surgery. We hypothesize that KLT has antitumor activity and immunomodulatory effects in Lewis lung carcinoma.

Materials and methods: C57BL/6 mice with Lewis lung carcinoma were divided into four groups: the control group (C), cisplatin group (1 mg/kg, DDP), low KLT group (6.25 ml/kg body weight [L]), and high KLT group (12.5 ml/kg body weight [H]). T cell proliferation was determined by the MTT assay. Nuclear factor-kappa B (NF-κB), inhibitor kappa B alpha (IκBα), IκB kinase (IKK) and epidermal growth factor receptor (EGFR) levels were measured by western blotting. An enzyme-linked immunosorbent assay was used to analyze the expression of interleukin-2 (IL-2).

Results: Intraperitoneal KLT significantly inhibited the growth of Lewis lung carcinoma, and the spleen index was significantly higher in the L and H groups than in the C group. KLT stimulated T cell proliferation in a dose-dependent manner. Treatment with KLT at either 6.25 or 12.5 ml/kg decreased the level of NF-κB in the nucleus in a dose-dependent manner, and KLT markedly decreased the expression of IκBα, IKK and EGFR in the cytoplasm of tumor cells and overall. IL-2 was significantly increased in the supernatant of splenocytes in the H group.

Conclusions: These results demonstrate that KLT has pronounced antitumor and immunostimulatory activities in C57BL/6 mice with Lewis lung carcinoma. These may affect the regulation of NF-κB/IκB expression, in addition to cytokines such as IL-2 and EGFR. Further work needs to investigate the relevant signaling pathway effects, but our findings suggest that KLT may be a promising antitumor drug for clinical use.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Carcinoma, Lewis Lung / drug therapy*
  • Carcinoma, Lewis Lung / metabolism
  • Carcinoma, Lewis Lung / pathology
  • Cell Proliferation / drug effects
  • Drugs, Chinese Herbal / administration & dosage*
  • ErbB Receptors / metabolism
  • I-kappa B Kinase / metabolism
  • I-kappa B Proteins / metabolism
  • Immunologic Factors / administration & dosage*
  • Injections, Intraperitoneal
  • Interleukin-2 / immunology
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism
  • Organ Size / drug effects
  • Spleen / drug effects
  • Spleen / metabolism
  • Spleen / pathology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Tumor Burden / drug effects

Substances

  • Antineoplastic Agents
  • Drugs, Chinese Herbal
  • I-kappa B Proteins
  • Immunologic Factors
  • Interleukin-2
  • NF-kappa B
  • Nfkbia protein, mouse
  • NF-KappaB Inhibitor alpha
  • ErbB Receptors
  • I-kappa B Kinase
  • kang-lai-te