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索拉非尼与 NK 细胞共注射联合治疗肝细胞癌的效果;一项体内研究方法

英文原题:The effects of Sorafenib and Natural killer cell co-injection in combinational treatment of hepatocellular carcinoma; an in vivo approach.

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The effects of Sorafenib and Natural killer cell co-injection in combinational treatment of hepatocellular carcinoma; an in vivo approach.

PubMed 2022/01/28(内容时间) Pharmacol Rep Q2 · IF 4.5(JCR 2025)

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研究概要

在 HCC 小鼠模型中,特定剂量的 NKC 与 Sor 联合治疗未能通过协同效应抑制 HCC 异种移植瘤的生长速率。

研究思路结论见上方概要

NK 细胞(NKC)和索拉非尼(Sor)是治疗肝细胞癌(HCC)的两种重要药物。在过去十年中,Sor与NKC联合抗HCC的相互作用一直备受挑战。本研究旨在评估NKC联合Sor在体内治疗HCC的疗效。

在裸鼠中建立了HCC的皮下异种移植模型。为了评估治疗的安全性,分析了肾脏和肝脏功能。对石蜡包埋的肿瘤切片进行了组织病理学研究,并进行了免疫组织化学(IHC)检测,以评估血管生成(CD34)和增殖(Ki67)指数。采用末端脱氧核苷酸转移酶dUTP缺口末端标记(TUNEL)法检测发生凋亡的肿瘤细胞。通过酶联免疫吸附试验(ELISA)测定血清中肿瘤坏死因子-α(TNF-α)和干扰素-γ(IFN-γ)水平,并使用实时PCR对异种移植HCC中主要炎性细胞因子和胞质颗粒的表达水平进行定量。

与单独使用NKC或Sor相比,NKC与Sor联合显著抑制了肿瘤细胞的坏死和凋亡,并增加了HCC的血管生成和增殖。在接受NKC与Sor联合治疗的异种移植HCC小鼠中,血清TNF-α、IFN-γ水平以及HCC组织中TNF-α、IFN-γ、白细胞介素(ILs)-1、6、10、颗粒酶-B和穿孔素的表达水平均显著低于单独使用NKC或Sor治疗的小鼠。

展开英文摘要原文

Natural killer cells (NKC) and Sorafenib (Sor) are two important agents for the treatment of hepatocellular carcinoma (HCC). Over the past decade, the interaction of Sor and NKC against HCC has been widely challenging. This study aimed to assess the efficacy of NKC & Sor for the treatment of HCC in vivo.

Subcutaneous xenograft models of HCC were established in nude mice. For safety assessment of treatment, the kidney and liver functions were analyzed. Paraffin embedded tumor sections were histopathologically studied and immunohistochemistry (IHC) tests were done to evaluate the angiogenesis (CD34) and proliferation (Ki67) indexes. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to identify the tumor cells undergoing apoptosis. The serum levels of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were measured by enzyme-linked immunosorbent assay (ELISA) and expression levels of major inflammatory cytokines and cytoplasmic granules in xenograft HCC were quantified using real-time PCR.

NKC & Sor significantly inhibited necrosis and apoptosis in tumor cells and increased angiogenesis and proliferation of HCC compared to the monotherapy of NKC or Sor alone. The serum levels of TNF-α, IFN-γ as well as the expression levels of TNF-α, IFN-γ, interleukins (ILs)-1, 6, 10, granzyme-B and perforin in the xenograft HCC tissues of the treated mice with NKC & Sor were significantly lower than those of treated with NKC or Sor alone.

Therapy with the specific dosage of NKC & Sor could not inhibit the HCC xenograft growth rate through a synergistic effect in a mouse model of HCC.

论文信息

作者
Hosseinzadeh F、Ai J、Hajifathali A、Muhammadnejad S、Ebrahimi-Barough S、Seyhoun I、Komeili Movahed T、Shirian S
第一作者单位
Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. f.hosseinzadeh@muq.ac.ir.Iran
通讯作者单位
Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. javad0verdi@gmail.com.Iran
期刊
Pharmacological reports : PR2022 Apr
原文标识
PubMed 35089543 · DOI 10.1007/s43440-021-00335-y