Adami Eliana Rezende, Corso Claudia Rita, Turin-Oliveira Natalia Mulinari, Galindo Claudia Martins, Milani Leticia, Stipp Maria Carolina, da Silva Liziane Cristine Malaquias, do Nascimento Georgia Erdmann, Chaves Pedro Felipe Pereira, Chequin Andressa, Mariott Marihá, da Silva Luisa Mota, Klassen Giseli, Ramos Edneia A S, Cordeiro Lucimara M C, Acco Alexandra
Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil; Department of Clinical Analysis, Federal University of Paraná, Curitiba, PR, Brazil.
Department of Pharmacology, Federal University of Paraná, Curitiba, PR, Brazil; Pelé Pequeno Príncipe Research Institute, Curitiba, PR, Brazil.
Int J Biol Macromol. 2020 May 5;158:1071-1081. doi: 10.1016/j.ijbiomac.2020.05.001.
This study investigated the antineoplastic effects and toxicity of long-term treatment with polysaccharides from sweet green pepper (Capsicum annuum [CAP]), and concomitant treatment with CAP + methotrexate (MTX) on mammary tumor cells in vivo and in vitro. Ehrlich tumor cells were subcutaneously inoculated in female Swiss mice. The long-term treatment (31 days) with CAP (100 mg kg, p.o.) reduced the tumor growth and did not induce toxicity. The combined treatment protocol of 100 mg kg CAP (p.o.) + 1 mg kg MTX (i.p.) for 21 days inhibited the tumor growth in 95%, higher than the inhibition induced by MTX alone (1.0 or 2.5 mg kg, i.p.). In tumors, both CAP and CAP + MTX decreased the gene expression of Vegf, vessel area, and IL-4 and IL-10 levels, and increased IL-6 levels and the degree of necrosis. Treatment with CAP + MTX also increased TNF-α levels in tumors. Additionally, CAP + MTX treatment reduced the viability of human MDA-MB-231 and MDA-MB-436 mammary tumor cells in culture. In fact, CAP exerted antineoplastic effects in vivo and in vitro against mammary tumor cells, possibly by modulating inflammation and angiogenesis. CAP may be a promising adjunct chemotherapy with lower toxicity.
本研究调查了甜青椒(辣椒属[CAP])多糖长期治疗的抗肿瘤作用和毒性,以及CAP与甲氨蝶呤(MTX)联合治疗对体内外乳腺肿瘤细胞的影响。将艾氏腹水癌细胞皮下接种于雌性瑞士小鼠体内。CAP(100mg/kg,口服)长期治疗(31天)可抑制肿瘤生长且未诱导毒性。100mg/kg CAP(口服)+1mg/kg MTX(腹腔注射)联合治疗方案持续21天,对肿瘤生长的抑制率达95%,高于单独使用MTX(1.0或2.5mg/kg,腹腔注射)所诱导的抑制率。在肿瘤组织中,CAP和CAP+MTX均可降低Vegf基因表达、血管面积以及IL-4和IL-10水平,并增加IL-6水平和坏死程度。CAP+MTX治疗还可提高肿瘤组织中的TNF-α水平。此外。CAP+MTX治疗可降低培养的人MDA-MB-231和MDA-MB-436乳腺肿瘤细胞的活力。事实上,CAP在体内外对乳腺肿瘤细胞均具有抗肿瘤作用,可能是通过调节炎症和血管生成实现的。CAP可能是一种毒性较低的有前景的辅助化疗药物。