Liedtke Kim-Rouven, Freund Eric, Hermes Maraike, Oswald Stefan, Heidecke Claus-Dieter, Partecke Lars-Ivo, Bekeschus Sander
Department of General, Visceral, Thoracic and Vascular Surgery, Greifswald University Medical Center, 17475 Greifswald, Germany.
Centre for Innovation Competence (ZIK) plasmatis, Leibniz Institute for Plasma Science and Technology (INP Greifswald), 17489 Greifswald, Germany.
Cancers (Basel). 2020 Jan 2;12(1):123. doi: 10.3390/cancers12010123.
Pancreatic cancer is one of the most aggressive tumor entities. Diffuse metastatic infiltration of vessels and the peritoneum restricts curative surgery. Standard chemotherapy protocols include the cytostatic drug gemcitabine with limited efficacy at considerable toxicity. In search of a more effective and less toxic treatment modality, we tested in human pancreatic cancer cells (MiaPaca and PaTuS) a novel combination therapy consisting of cytostatic drugs (gemcitabine or cisplatin) and gas plasma-conditioned Ringer's lactate that acts via reactive oxygen species. A decrease in metabolic activity and viability, change in morphology, and cell cycle arrest was observed in vitro. The combination treatment was found to be additively toxic. The findings were validated utilizing an in ovo tumor model of solid pancreatic tumors growing on the chorion-allantois membrane of fertilized chicken eggs (TUM-CAM). The combination of the drugs (especially cisplatin) with the plasma-conditioned liquid significantly enhanced the anti-cancer effects, resulting in the induction of cell death, cell cycle arrest, and inhibition of cell growth with both of the cell lines tested. In conclusion, our novel combination approach may be a promising new avenue to increase the tolerability and efficacy of locally applied chemotherapeutic in diffuse metastatic peritoneal carcinomatosis of the pancreas.
胰腺癌是侵袭性最强的肿瘤类型之一。血管和腹膜的弥漫性转移浸润限制了根治性手术。标准化疗方案包括细胞毒性药物吉西他滨，但其疗效有限且毒性较大。为了寻找一种更有效且毒性更小的治疗方式，我们在人胰腺癌细胞（MiaPaca和PaTuS）中测试了一种由细胞毒性药物（吉西他滨或顺铂）和经气体等离子体处理的乳酸林格氏液组成的新型联合疗法，该疗法通过活性氧发挥作用。在体外观察到代谢活性和活力降低、形态改变以及细胞周期停滞。发现联合治疗具有相加毒性。利用在受精鸡蛋的绒毛尿囊膜上生长的实体胰腺肿瘤的卵内肿瘤模型（TUM-CAM）验证了这些发现。药物（尤其是顺铂）与经等离子体处理的液体联合使用显著增强了抗癌效果，导致所测试的两种细胞系均出现细胞死亡、细胞周期停滞和细胞生长抑制。总之，我们的新型联合方法可能是一种有前景的新途径，可提高局部应用化疗药物治疗胰腺弥漫性转移性腹膜癌的耐受性和疗效。
