Cancer Chemotherapy and Pharmacology

, Volume 66, Issue 5, pp 981–986

Antitumor effects of recombinant human Interleukin-6 on mouse bladder carcinoma through Fas-mediated apoptosis

  • Chuan-gang Li
  • Mo-lin Li
  • Xiao-hong Shu
  • Yong-ji Liu
  • Wen-sen Wu
Original Article

DOI: 10.1007/s00280-010-1336-7

Cite this article as:
Li, C., Li, M., Shu, X. et al. Cancer Chemother Pharmacol (2010) 66: 981. doi:10.1007/s00280-010-1336-7

Abstract

Purpose

An apoptosis-inducing therapy is gradually becoming a new strategy for cancer treatment. The aim of this study was to investigate the mechanism of growth-inhibitory effects of recombinant human interleukin-6 (rhIL-6) on bladder tumor-bearing T739 mice in vivo.

Methods

Murine bladder transitional carcinoma cells (BTT739) were inoculated subcutaneously into T739 mice as a tumor model for evaluating the antitumor effects of rhIL-6. Then the mice were divided randomly into 5 groups: A, B, C, D and E. Different doses (0, 2, 4, 8 × 106 IU/kg body weight) of rhIL-6 were injected intraperitoneally twice per day and administered for 14 days, and 1 mg/kg/d mitomycin-C(MMC) was used as control. Tumor size was measured and determined as the mean of the largest diameter and the diameter at right angle. Animals were killed by CO2 inhalation on the 15th day after tumor cell inoculation. Then, tumors were removed, weighed and collected. The tumor growth inhibition rate of rhIL-6 was calculated. The morphological characteristic changes of tumor cells were observed under electron microscope, and cell cycle analysis was determined by flow cytometry. The expressions of Fas, FasL and Bcl-2 protein on tumor cells were qualitatively detected by immunofluorescence cell staining, and their relative contents (rate of positive cells, RPC) were quantitatively determined with flow cytometry.

Results

rhIL-6 could inhibit bladder tumor growth in a dose-dependent manner in vivo. The tumor growth-inhibitory rates of 2, 4, 8 × 106 IU/kg rhIL-6 and 1 mg/kg MMC were 11.8, 39.5, 39.7 and 68.8%, respectively. Flow cytometry results showed that a hypodiploid peak before G1 phase could be found in tumor cells treated with rhIL-6. Moreover, the cells treated with rhIL-6 displayed disappearance of nucleoli, chromatin gathering under the nuclear membrane in mass or ring-shape under transmission electron microscopy. The rates of Fas, FasL protein–positive cells estimated by flow cytometry in rhIL-6-treated mice were (12.57 ± 0.83) and (20.1 ± 0.87) %, respectively, significantly higher than that (4.66 ± 0.17) and (14.1 ± 0.83) % in control mice (P < 0.01). There was no significant difference in the rate of Bcl-2 protein–positive cells between the mice in these two groups (P > 0.05).

Conclusions

rhIL-6 had obvious antitumor effects on mouse bladder carcinoma in vivo, and the Fas signaling pathway might play an important role in rhIL-6-induced bladder carcinoma cell apoptosis.

Keywords

Recombinant human interleukin-6 (rhIL-6) Bladder cancer Fas Apoptosis T739 mice 

Abbreviations

rhIL-6

Recombinant human interleukin-6

IL-6

Interleukin-6

MMC

Mitomycin-C

BTT739

Murine bladder transitional carcinoma cells

PBS

Phosphate-buffered saline

PI

Propidium Iodide

i.p.

Intraperitoneally

FADD

Fas-associated death domain

RPC

Rate of positive cells

TEM

Transmission electron microscopy

SPSS

Statistical package for social science

SD

Standard deviation

LSD

Least significant difference

ANOVA

Analysis of variance

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Chuan-gang Li
    • 1
  • Mo-lin Li
    • 2
  • Xiao-hong Shu
    • 2
  • Yong-ji Liu
    • 1
  • Wen-sen Wu
    • 3
  1. 1.The Second Affiliated HospitalDalian Medical UniversityDalianPeople’s Republic of China
  2. 2.Dalian Medical UniversityDalianPeople’s Republic of China
  3. 3.The First People’s Hospital of ShanghaiShanghaiPeople’s Republic of China

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