Low dose suramin as a chemosensitizer of bladder cancer to mitomycin C
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Updated: Aug 17, 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
Yan Xin1, Greg Lyness, Danny Chen
1College of Pharmacy, James Cancer Hospital and Solove Research Institute, Ohio State University, Columbus, Ohio, USA.
Purpose:
We have reported that acidic and basic fibroblast growth factors expressed in solid tumors induce broad-spectrum chemoresistance and their nonspecific inhibitor suramin (Sigma Chemical Co., St. Louis, Missouri) at nontoxic concentrations enhances the activity of chemotherapeutic agents. In the current study we evaluated whether low dose suramin enhances tumor sensitivity to mitomycin C (MMC) (Bristol-Myer Squibb Co., Wallingford, Connecticut).
Materials And Methods:
Three-dimensional histocultures of RT4 (American Type Culture Collection, Rockville, Maryland) xenograft tumors and tumors from patients with bladder cancer were treated with MMC with or without 20 microM suramin. For in vivo studies mice bearing RT4 tumors received physiological saline, MMC (3 mg/kg), suramin (10 mg/kg) or MMC/suramin combination every 3 or 4 days. Two MMC schedules were studied, namely subtherapeutic (3 treatments) and therapeutic (6 treatments) schedules.
Results:
Suramin enhanced MMC activity in xenograft and patient tumor histocultures by greater than 2-fold. The chemosensitization effect was observed in all patient tumors (2 superficial and 9 muscle invading lesions). In animals tumors in the control and suramin groups increased to approximately 3 to 5 times the initial size. The subtherapeutic MMC schedule retarded tumor growth but did not produce tumor shrinkage, whereas the therapeutic MMC schedule reduced tumor size by 27%. The addition of suramin enhanced MMC activity. Respective tumor sizes were 40% and 63% of the sizes after subtherapeutic and therapeutic MMC alone (p <0.01). The combination groups showed body weight losses similar to those of MMC alone.
Conclusions:
Low dose suramin enhanced the in vitro and in vivo activity of subtherapeutic and therapeutic MMC without enhancing host toxicity, thus, providing proof of concept for evaluating low dose suramin as a chemosensitizer with MMC in bladder cancer.
Insights
Low dose suramin enhances mitomycin C (MMC) chemotherapy effectiveness against bladder cancer. This study demonstrates suramin as a potential chemosensitizer, improving MMC
Area of Science:
- Oncology
- Pharmacology
Background:
- Acidic and basic fibroblast growth factors in tumors can cause chemoresistance.
- Suramin, a nonspecific inhibitor, has shown potential to enhance chemotherapy activity.
- Previous research indicated suramin's ability to improve chemotherapeutic agent efficacy.
Purpose of the Study:
- To evaluate if low-dose suramin can enhance tumor sensitivity to mitomycin C (MMC).
Main Methods:
- Three-dimensional histocultures of RT4 xenograft and human bladder tumors were treated with MMC and suramin.
- In vivo studies involved mice bearing RT4 tumors, treated with MMC alone or in combination with suramin.
- Two MMC treatment schedules were used: subtherapeutic (3 treatments) and therapeutic (6 treatments).
Main Results:
- Suramin more than doubled MMC activity in both xenograft and patient tumor histocultures.
- In vivo, suramin significantly enhanced MMC's tumor-retarding and tumor-shrinking effects.
- Tumor sizes were reduced to 40% and 63% of control with subtherapeutic and therapeutic MMC plus suramin, respectively.
- No increased host toxicity was observed with the combination therapy.
Conclusions:
- Low-dose suramin effectively enhanced both in vitro and in vivo activity of mitomycin C.
- This study provides proof of concept for using low-dose suramin as a chemosensitizer with MMC in bladder cancer treatment.
- Suramin demonstrated enhanced efficacy without increasing host toxicity.
