Department of Carcinogenesis and Oncogerontology, N.N. Petrov National Medical Research Center of Oncology, 68, Leningradskaya Str., Pesochny, Saint Petersburg 197758, Russia; Nobel Ltd., of. 333, 271A, pr. Obukhovskoy Oborony, Saint Petersburg 192012, Russia.
Department of Carcinogenesis and Oncogerontology, N.N. Petrov National Medical Research Center of Oncology, 68, Leningradskaya Str., Pesochny, Saint Petersburg 197758, Russia.
J Trace Elem Med Biol. 2022 Sep;73:127013. doi: 10.1016/j.jtemb.2022.127013. Epub 2022 May 31.
A standard approach to study the anticancer activity of novel drugs is their testing in animals with inoculated tumors, which has some limitations. An alternative is the use of spontaneous or carcinogen-induced tumor models as they have better translation potential. The carcinogen-induced and transgenic tumor models were used to assess the antitumor activity of BP-C1, a platinum-containing drug with lignin-derived polymeric ligand.
We used female Swiss-H-derived mice and Wistar female rats to induce autochthonous tumors via exposure to benzo[a]pyrene and 1,2-dimethylhydrazine, respectively. Additionally, transgenic HER-2/neu FVB/N female mice, prone to the development of spontaneous mammary carcinomas, were used.
Antitumor activity of BP-C1 was observed in soft tissue sarcomas, induced by benzo[a]pyrene. The animals treated with BP-C1 exhibited more stabilizations and therapy responses compared to placebo controls. The efficacy of BP-C1 was somewhat reduced compared to cyclophosphamide; however, their combination resulted in an enhanced antitumor effect. For the 1,2-dimethylhydrazine-induced rat colon cancer model, BP-C1 reduced tumor multiplicity by 21-41 %. For mammary adenocarcinomas in HER-2/neu FVB/N mice, short-termed complete responses were observed in the BP-C1 groups with a frequency of 12-13 %, while complete responses were absent in the placebo group.
The results acquired indicated a wide spectrum of antitumor activity of BP-C1.
研究新型药物抗癌活性的标准方法是在接种肿瘤的动物中进行测试，但这种方法存在一些局限性。另一种方法是使用自发或致癌剂诱导的肿瘤模型，因为它们具有更好的转化潜力。本研究使用致癌剂诱导和转基因肿瘤模型来评估 BP-C1 的抗肿瘤活性，BP-C1 是一种含有木质素衍生聚合配体的含铂药物。
我们分别使用雌性瑞士-H 衍生小鼠和 Wistar 雌性大鼠，通过苯并[a]芘和 1,2-二甲基肼暴露来诱导同源肿瘤。此外，还使用了易发生自发性乳腺癌的 HER-2/neu FVB/N 转基因雌性小鼠。
BP-C1 在苯并[a]芘诱导的软组织肉瘤中表现出抗肿瘤活性。与安慰剂对照组相比，接受 BP-C1 治疗的动物表现出更多的稳定和治疗反应。与环磷酰胺相比，BP-C1 的疗效有所降低；然而，它们的联合使用导致了增强的抗肿瘤效果。对于 1,2-二甲基肼诱导的大鼠结肠癌模型，BP-C1 使肿瘤多发性降低了 21-41%。对于 HER-2/neu FVB/N 小鼠的乳腺腺癌，BP-C1 组观察到短期完全缓解的频率为 12-13%，而安慰剂组则没有完全缓解。
研究结果表明 BP-C1 具有广泛的抗肿瘤活性。
