Department of Biology, College of Science, Salahaddin University-Erbil, Erbil, Kurdistan Region, 44002, Iraq.
Department of Medical Laboratory Technology, Health Technical College, Erbil Polytechnic University, Erbil, Iraq.
Sci Rep. 2021 Jan 28;11(1):2536. doi: 10.1038/s41598-021-82244-x.
This study was carried out to assess the impact of nickel nanoparticles (NiNPs) as well as scorpion venom on colorectal cancer (CRC) cells in the presence and/or absence of 5-fluorouracil (5-FU), hydrogen sulfide (HS), and nitric oxide (NO) donors and to determine alterations in endothelial NO synthase (eNOS) and cystathionine γ-lyase (CSE) enzyme-producing genes in CRC patients. The IC of both HS and NO donors, along with NiNPs, were determined. The CRC cells were treated for 24hrs, and the cytotoxic activities were assessed using the MTT test. Moreover, the apoptosis was determined after 24hrs and 48hrs using TUNEL assay. Furthermore, the mutations in the eNOS gene (intron 4, -786T>C and 894 G>T) and CSE gene (1364GT) were determined using direct sequencing. The IC values for sodium disulfide (NaS) and sodium nitroprusside (SNP) at 24hrs treatment were found to be 5 mM and 10 M, respectively, while the IC value for 5-FU was reached after 5-days of treatment in CRC cell line. Both black and yellow scorpion venoms showed no inhibition of cell proliferation after 24hrs treatment. Furthermore, NaS showed a significant decrease in cell proliferation and an increase in apoptosis. Moreover, a co-treatment of SNP and 5-FU resulted in inhibition of the cytotoxic effect of 5-FU, while a combination treatment of NiNPs with NaS, SNP, and 5-FU caused highly significant cytotoxicity. Direct sequencing reveals new mutations, mainly intronic variation in eNOS gene that has not previously been described in the database. These findings indicate that HS promotes the anticancer efficiency of 5-FU in the presence of NiNPs while NO has antiapoptotic activity in CRC cell lines.
本研究旨在评估镍纳米粒子（NiNPs）以及蝎子毒液在存在和/或不存在 5-氟尿嘧啶（5-FU）、硫化氢（HS）和一氧化氮（NO）供体的情况下对结直肠癌（CRC）细胞的影响，并确定 CRC 患者中内皮型一氧化氮合酶（eNOS）和胱硫醚 γ-裂解酶（CSE）产生基因的改变。确定了 HS 和 NO 供体以及 NiNPs 的 IC。将 CRC 细胞处理 24 小时，并使用 MTT 试验评估细胞毒性活性。此外，在 24 小时和 48 小时使用 TUNEL 测定法测定细胞凋亡。此外，使用直接测序确定 eNOS 基因（内含子 4、-786T>C 和 894 G>T）和 CSE 基因（1364GT）的突变。发现 24 小时处理时硫代硫酸钠（NaS）和硝普酸钠（SNP）的 IC 值分别为 5 mM 和 10 μM，而 5-FU 的 IC 值在 CRC 细胞系中经过 5 天的治疗后达到。黑色和黄色蝎子毒液在 24 小时处理后均未显示出对细胞增殖的抑制作用。此外，NaS 显示出细胞增殖的显著减少和凋亡的增加。此外，SNP 和 5-FU 的共同处理导致 5-FU 的细胞毒性作用受到抑制，而 NiNPs 与 NaS、SNP 和 5-FU 的组合处理导致高度显著的细胞毒性。直接测序揭示了新的突变，主要是 eNOS 基因的内含子变异，这些变异以前在数据库中尚未描述过。这些发现表明，HS 在 NiNPs 存在的情况下促进了 5-FU 的抗癌效率，而 NO 在 CRC 细胞系中具有抗凋亡活性。
