Prevention of Peritoneal Carcinomatosis in Mice by Combining Hyperthermal Intraperitoneal Chemotherapy with the Water Extract from Burr Parsley (Caucalis platycarpos L.)

Abstract

The presence of peritoneal carcinomatosis arising from gastrointestinal and gynecologic tumors is associated with a poor prognosis. Animal models of peritoneal carcinomatosis are important in the evaluation of new treatment modalities. The purpose of this study was to investigate the effect of local chemoimmunotherapy and hyperthermal intraperitoneal chemotherapy (HIPEC) in an animal model of induced peritoneal carcinomatosis in the mouse. For induction of peritoneal carcinomatosis, cells from transplantable mammary carcinoma (MCa) were implanted intraperitoneally in CBA mice. Seven or 3 days before implantation of MCa cells (5 × 10³) the mice were injected with lyophilized water extract from Caucalis platycarpos L. (CPL; 200 mg · kg⁻¹) into the abdominal cavity. Immediately after implantation of MCa cells in the abdominal cavity, mice were treated two times with 2 mL of saline that was heated either at 37 °C or 43 °C (hyperthermal treatment) and cytostatics (doxorubicin 20 mg · kg⁻¹, cisplatin 10 mg · kg⁻¹, mitomycin 5 mg · kg⁻¹, 5-FU 150 mg · kg⁻¹). We followed the survival of animals and the side effects appearing with different forms of treatment. CPL increased the life span of mice with peritoneal carcinomatosis without hyperthermal treatment (ILS% = 32.55 %) but showed no effect on the life span of mice with hyperthermal treatment (ILS% = 1.44). Combined treatment with CPL and cytostatics (CIS, DOX, and MIT) significantly affected the development of peritoneal carcinomatosis and increased the survival of mice (ILS% – 37 °C = 144.17, 415.46, and 124.13, ILS% – 43 °C = 311.42, 200.74, and 138.33, respectively). However, intraperitoneal chemotherapy with 5-FU alone resulted in greater survival time of mice than the treatment with 5-FU + CPL. Results suggest the synergistic effect of hyperthermia, chemotherapy, and immunotherapy. CPL significantly increases the antitumor activity of the hyperthermic chemotherapy and the survival rate of mice with peritoneal carcinomatosis. The stimulative effect of CPL on immunomodulation may be a possible mechanism which protects mice from developing peritoneal carcinomatosis and reduces the side effects of chemotherapy, increasing the life span of mice.

Key words

Caucalis platycarpos L. - Apiaceae - hyperthermia - chemotherapy - peritoneal carcinomatosis - mouse

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