纳米金刚石共轭槲皮素对结肠癌的抗转移作用:一项体内研究。

Turkish journal of biology = Turk biyoloji dergisi Pub Date : 2024-09-17 eCollection Date: 2024-01-01 DOI:10.55730/1300-0152.2704
Firli Rahmah Primula Dewi, Sephia Tiara Marviella, Sri Puji Astuti Wahyuningsih, A'liyatur Rosyidah, Vuanghao Lim, Lionel Lian Aun In, Amy Yi Hsan Saik, Bimaji Ariyogo, Mee Lee Looi
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引用次数: 0

摘要

背景/目的:槲皮素(Q)是一种可抑制结肠癌细胞生长的化合物;然而,要做到这一点,需要高剂量,需要一种可直接靶向癌内皮细胞的给药系统。本研究探讨了纳米金刚石共轭槲皮素(NDQ)作为抗癌药物对 N-甲基亚硝基脲(MNU)诱导的鼠结肠癌的有效性:本研究以实验为基础,设计了六组处理方法,即正常对照(KN:不经MNU、纳米金刚石(ND)或Q处理);阴性对照(K-:经MNU处理);阳性对照(K+:经MNU和卡培他滨处理);ND(经MNU和NDs处理);Q(经MNU和Q处理);NDQ(经MNU和NDQ处理)。为了诱发大鼠结肠癌,每周三次直肠内注射 MNU(10 毫克/千克体重),连续注射四周。腹腔注射 Q(40 毫克/千克体重)或 NDQ(40 毫克/千克体重),每周两次,连续 6 周。通过测量体重和结肠重量来评估所有组群的癌症进展情况,其中包括以下内容:转移标志物基质金属蛋白-9(MMP-9)、癌胚抗原(CEA)、低氧诱导因子1α(HIF1α)、血管内皮生长因子、蛋白53(p53)的特异性酶联免疫吸附试验以及Caspase-3和Ki-67蛋白的免疫组化染色。同时还观察了癌症向肺部转移的情况:结果:与K组相比,NDQ能明显抑制癌症的侵袭性,使体重增加和生长速度加快,同时减轻结肠重量。此外,与 Q 组相比,NDQ 组 MMP-9、CEA、HIF-1α 和 Ki67 水平的降低以及 p53 和 Caspase-3 水平的升高更为明显。NDQ组的肺部肿瘤转移少于K组:结论:NDQ提高了Q的抗癌活性,表明NDs具有有效的给药特性。
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Antimetastatic effect of nanodiamond-conjugated quercetin against colon cancer: an in vivo study.

Background/aim: Quercetin (Q) is a compound that can inhibit the growth of cancer cells in the colon; however, to do so, a high dose is needed, requiring a drug delivery system to target cancer endothelial cells directly. This study investigates the potency of nanodiamond-conjugated quercetin (NDQ) as an anticancer drug against colon cancer in Rattus norvegicus induced by N-methyl N-Nitrosourea (MNU).

Materials and methods: This study is experimental-based and was designed using a six-group treatment method, namely normal control (KN: not treated by MNU, nanodiamond (ND), or Q); negative control (K-: treated by MNU); positive control (K+: treated by MNU and capecitabine); ND (treated by MNU and NDs); Q (treated by MNU and Q); and NDQ (treated by MNU and NDQ). To induce colon cancer in rats, MNU (10 mg/Kg BW) was administrated intrarectally three times per week for four weeks. The treatment of Q (40 mg/Kg BW) or NDQ (40 mg/Kg BW) was given intraperitoneally twice a week for 6 weeks. Cancer progression of all cohorts was evaluated by performing body and colon weight measurements, which involved the following: ELISA assay-specific to metastatic marker matrix metalloprotein-9 (MMP-9), carcinoembryonic antigen (CEA), hypoxia-inducible factor 1 α (HIF1α), vascular endothelial growth factor, protein 53 (p53) and immunohistochemistry staining of Caspase-3 and Ki-67 proteins. Observation of cancer metastasis to the lung was also performed.

Results: NDQ significantly inhibited cancer aggressiveness by causing an increment in body weight gain and the growth rate-while reducing the colon weight compared to the K- group. Moreover, decreased levels of MMP-9, CEA, HIF-1α, and Ki67 and increased levels of p53 and Caspase-3 were more significant in the NDQ group than in the Q group. The lung tumor metastases in the NDQ group were fewer than in the K- group.

Conclusion: NDQ increased Q's anticancer activity, suggesting that NDs have an effective drug delivery property.

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