Antitumor and immunomodulatory effects of low-dose 5-FU on hepatoma 22 tumor-bearing mice

Abstract

Low-dose 5-fluorouracil (5-FU), a widely used chemotherapeutic, has been reported to have immunomodulatory effects. This study aimed to evaluate the optimal dose of 5-FU that produces antitumor and immunomodulatory effects. In a hepatoma 22 tumor-bearing mouse model, 0, 10, 20 and 40 mg/kg 5-FU (i.p.) was administered for 10 days. Tumor weight and volume were measured, thymus index (TI) and spleen index (SI) were calculated, and the number of white blood cells (WBCs) and lymphocytes (LYs) were counted following treatment. The percentages of CD3+, CD4+, CD8+ and natural killer (NK) cells were measured by flow cytometry. In addition, the body weights of the mice were measured and the average diet consumption was calculated. Administration of 5-FU produced a potent antitumor effect in a dose-dependent manner (P<0.01). At 20 and 40 mg/kg, a significant reduction of body weight and food consumption was observed. TI and SI decreased in the 20- and 40-mg/kg groups (P<0.01) for 10 days. The number of WBCs significantly decreased in each group (P<0.01); however, the number of LYs only decreased in the 40-mg/kg group (P<0.01). Percentages of CD3+ and CD4+ cells were increased in the 10- and 20-mg/kg groups (P<0.01). Thus, 5-FU at 10 mg/kg inhibits tumor growth while maintaining the immune function of the mice. 5-FU may exert its antitumor effect at a low dose with low toxicity and stimulate the host immune system. Future clinical trials taking into account the immunostimulatory capacity of chemotherapeutic agents are desirable for certain patients.

Chemotherapy but not the tumor draining lymph nodes determine the immunotherapy response in secondary tumors

“…In addition to the time window, the dose is another potential factor that affects the chemotherapy-induced immune response. Low dose chemotherapies have shown special immunoregulatory effects in tumor models 50,51 . Further studies are warranted to tests different chemotherapy doses on the chemo-immunotherapy combination.…”

Gastrointestinal dysfunction and enteric neurotoxicity following treatment with anticancer chemotherapeutic agent 5‐fluorouracil

“…The dose of 5‐FU was calculated to be equivalent to standard human dose per body surface area . The low doses of 5‐FU (10–40 mg/kg) have been shown to have antitumor efficacy in mouse models of cancer . Sham‐treated mice received 10% DMSO in sterile water via intraperitoneal injection three times a week via a 26 gauge needle.…”

“…17 The low doses of 5-FU (10-40 mg/kg) have been shown to have antitumor efficacy in mouse models of cancer. 18 Sham-treated mice received 10% DMSO in sterile water via intraperitoneal injection three times a week via a 26 gauge needle. The injected volumes were calculated to the body weight; the maximum volume did not exceed 200 lL per injection.…”

5-Fluoruracil blocked giant cell tumor progression by suppressing osteoclastogenesis through NF-kappaB signals and blocking angiogenesis

“…5-FU shows positive results in many solid tumors, such as gastrointestinal malignancies and hepatoma [39,40]. As a commonly prescribed chemotherapy agents, its efficacy and safety have been proved in many clinical trials [24][25][26].…”