1 N.N. Petrov National Medical Research Center of Oncology, Saint Petersburg, Russia.
2 Nobel Ltd, Saint Petersburg, Russia.
Integr Cancer Ther. 2019 Jan-Dec;18:1534735419833778. doi: 10.1177/1534735419833778.
This study aimed to evaluate the effect of lignin-derived polyphenolic composition BP-C3 on the efficacy and hematological toxicity of cyclophosphamide (CPA). Male and female Swiss-H derived mice bearing benzo[a]pyrene-induced soft tissue sarcomas were treated with CPA 300 mg/kg, BP-C3 75 mg/kg, or a combination. Tumor growth inhibition in male mice treated with CPA, BP-C3, or a combination of CPA and BP-C3 was significant and corresponded to 78%, 45%, and 82%, respectively, on day 21 after CPA administration on day 0. In female mice, tumor growth inhibition was 58%, -11%, and 35% when treated with CPA, BP-C3, or a combination of CPA and BP-C3, respectively. CPA administration resulted in significant hematological toxicity evidenced by a decreased white blood cell count on day 4 (2.43 ± 1.77 × 10/L in male mice and 1.19 ± 0.71 × 10/L in female mice) and anemia development on day 7 (6.55 ± 1.74 × 10/L in male mice and 5.89 ± 2.24 × 10/L in female mice). The red blood cell count measured on day 7 in animals treated with the combination of BP-C3 and CPA constituted 7.12 ± 1.17 × 10/L and 7.36 ± 2.07 × 10/L for male and female mice, respectively. The results of our study demonstrate the antitumor activity of BP-C3 in male mice bearing soft tissue sarcomas. Neither the antitumor activity nor the hematological toxicity of CPA were significantly influenced by BP-C3. A less pronounced effect of CPA on RBC count is demonstrated when this agent is given jointly with BP-C3.
本研究旨在评估木质素衍生多酚组成物 BP-C3 对环磷酰胺（CPA）疗效和血液毒性的影响。雄性和雌性瑞士-H 衍生小鼠患有苯并[a]芘诱导的软组织肉瘤，用 300mg/kg 的环磷酰胺（CPA）、75mg/kg 的 BP-C3 或二者的组合进行治疗。雄性小鼠用 CPA、BP-C3 或 CPA 和 BP-C3 的组合治疗后，肿瘤生长抑制明显，分别在第 0 天给予 CPA 后第 21 天达到 78%、45%和 82%。在雌性小鼠中，分别用 CPA、BP-C3 或 CPA 和 BP-C3 的组合治疗后，肿瘤生长抑制分别为 58%、-11%和 35%。CPA 给药导致明显的血液毒性，表现为第 4 天白细胞计数减少（雄性小鼠为 2.43±1.77×10/L，雌性小鼠为 1.19±0.71×10/L）和第 7 天贫血发展（雄性小鼠为 6.55±1.74×10/L，雌性小鼠为 5.89±2.24×10/L）。用 BP-C3 和 CPA 组合治疗的动物在第 7 天测量的红细胞计数分别为雄性小鼠 7.12±1.17×10/L和雌性小鼠 7.36±2.07×10/L。我们的研究结果表明，BP-C3 在患有软组织肉瘤的雄性小鼠中具有抗肿瘤活性。BP-C3 既不影响 CPA 的抗肿瘤活性，也不影响其血液毒性。当该药物与 BP-C3 联合使用时，CPA 对 RBC 计数的影响不那么明显。
