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Updated: Jun 12, 2026
Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 30, 2013
Antitumor effects of recombinant human interleukin-6 on mouse bladder carcinoma through Fas-mediated apoptosis
Chuan-gang Li1, Mo-lin Li, Xiao-hong Shu
1The Second Affiliated Hospital, Dalian Medical University, Dalian, People's Republic of China.
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 x 10(6) 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 CO(2) 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 x 10(6) 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.
Insights
Recombinant human interleukin-6 (rhIL-6) effectively inhibits bladder tumor growth in mice. This apoptosis-inducing therapy activates the Fas signaling pathway, offering a potential new strategy for cancer treatment.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Apoptosis-inducing therapies are emerging as a key strategy in cancer treatment.
- Recombinant human interleukin-6 (rhIL-6) is being investigated for its potential antitumor properties.
Purpose of the Study:
- To investigate the mechanism of growth-inhibitory effects of rhIL-6 on bladder tumor-bearing mice.
- To evaluate the antitumor efficacy of rhIL-6 in vivo.
Main Methods:
- A mouse model of bladder transitional carcinoma was established using BTT739 cells.
- Mice were treated with varying doses of rhIL-6 or mitomycin-C (MMC).
- Tumor growth, cell morphology, cell cycle, and protein expression (Fas, FasL, Bcl-2) were analyzed.
Main Results:
- rhIL-6 demonstrated dose-dependent inhibition of bladder tumor growth.
- rhIL-6 treatment induced apoptosis, evidenced by a hypodiploid peak and morphological changes.
- Increased expression of Fas and FasL proteins was observed in rhIL-6 treated tumors, while Bcl-2 expression remained unchanged.
Conclusions:
- rhIL-6 exhibits significant antitumor effects against mouse bladder carcinoma in vivo.
- The Fas signaling pathway appears to be crucial in rhIL-6-mediated apoptosis of bladder cancer cells.
- rhIL-6 represents a promising candidate for novel cancer therapies.
