Dewi Firli Rahmah Primula, Marviella Sephia Tiara, Wahyuningsih Sri Puji Astuti, Rosyidah A'liyatur, Lim Vuanghao, In Lionel Lian Aun, Saik Amy Yi Hsan, Ariyogo Bimaji, Looi Mee Lee
Department of Biology, Faculty of Science and Technology, Universitas Airlangga, Surabaya, Indonesia.
Research Center for Vaccine and Drug, National Research and Innovation Agency, Bogor, Indonesia.
Turk J Biol. 2024 Sep 17;48(5):279-289. doi: 10.55730/1300-0152.2704. eCollection 2024.
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 induced by N-methyl N-Nitrosourea (MNU).
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.
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.
NDQ increased Q's anticancer activity, suggesting that NDs have an effective drug delivery property.
背景/目的:槲皮素(Q)是一种能够抑制结肠癌细胞生长的化合物;然而,要实现这一效果需要高剂量,因此需要一种药物递送系统来直接靶向癌内皮细胞。本研究调查了纳米金刚石偶联槲皮素(NDQ)作为一种抗癌药物对N-甲基-N-亚硝基脲(MNU)诱导的结肠癌的疗效。
本研究基于实验,采用六组治疗方法设计,即正常对照组(KN:未用MNU、纳米金刚石(ND)或Q处理);阴性对照组(K-:用MNU处理);阳性对照组(K+:用MNU和卡培他滨处理);ND组(用MNU和NDs处理);Q组(用MNU和Q处理);以及NDQ组(用MNU和NDQ处理)。为诱导大鼠患结肠癌,每周经直肠给予MNU(10mg/Kg体重)3次,共4周。Q(40mg/Kg体重)或NDQ(40mg/Kg体重)的治疗每周经腹腔给予2次,共6周。通过测量体重和结肠重量来评估所有队列的癌症进展,这包括以下内容:针对转移标志物基质金属蛋白酶-9(MMP-9)、癌胚抗原(CEA)、缺氧诱导因子1α(HIF1α)、血管内皮生长因子、蛋白53(p53)的ELISA检测以及Caspase-3和Ki-67蛋白的免疫组织化学染色。还进行了癌症向肺转移的观察。
与K-组相比,NDQ通过增加体重增加和生长速率同时降低结肠重量,显著抑制了癌症侵袭性。此外,NDQ组中MMP-9、CEA、HIF-1α和Ki67水平降低以及p53和Caspase-3水平升高比Q组更显著。NDQ组的肺肿瘤转移比K-组少。
NDQ增强了Q的抗癌活性,表明NDs具有有效的药物递送特性。