Selim Nabil M, El-Hawary Seham S, El Zalabani Soheir M, Shamma Rehab Nabil, Mahdy Nariman El Sayed, Sherif Noheir H, Youssif Khayrya A, Ramadan Abdelmohsen Usama, Mekkawy Mai H, Fahmy Hanan A
Faculty of Pharmacy, Cairo University, Cairo, Egypt.
National Centre for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Egypt.
Integr Cancer Ther. 2025 Jan-Dec;24:15347354241308858. doi: 10.1177/15347354241308858.
Hepatocellular carcinoma (HCC) represents the third-most prevalent cancer in humans worldwide. The current study's objective is to search for the potentiality of H. Wendl () leaf extract in a nanoemulsion (NE) form in enhancing radiotherapy against HCC induced in rats using diethylnitrosamine (DEN).
The metabolic composition of the bioactive extract of leaves was investigated by LC-MS. Oral epithelial (OEC) and liver carcinoma (HepG2) cell lines were used to examine the safety and anticancer activity of the NE, respectively. In the in vivo study, HCC was induced in male albino rats through administration of DEN in drinking water for 8 weeks, then treatment with NE (100 mg/kg) until the experiment's ending. Rats were irradiated by a fractionated dose of 2Gy*4.
NE exerted remarkable cytotoxicity in comparison to the parent extract and the standard doxorubicin on the HepG2 cell line. Besides, the NE administration and/or γ-irradiation (IRR) significantly reduced the elevated alanine aminotransferase (ALT), total proteins, and albumin levels in HCC-induced rats. Likewise, the tumor markers alpha-fetoprotein (AFP) and gamma-glutamyl transferase (GGT) levels were considerably reduced in HCC rats. In addition, NE treatment before IRR significantly decreased the expression of the poly ADP ribose polymerase-1 PARP1) enzyme and Ki67. Furthermore, the histological investigations strongly confirmed the combined effect of NE and IRR in fighting DEN-induced HCC.
NE of extract may possess a radiosensitizing novel impact and provide a new strategy to combat HCC in clinical practices.
肝细胞癌（HCC）是全球人类中第三大常见癌症。本研究的目的是探寻纳米乳剂（NE）形式的H. Wendl（）叶提取物增强对二乙基亚硝胺（DEN）诱导的大鼠肝癌放疗效果的潜力。
通过液相色谱 - 质谱联用仪研究叶生物活性提取物的代谢成分。分别使用口腔上皮（OEC）细胞系和肝癌（HepG2）细胞系检测NE的安全性和抗癌活性。在体内研究中，通过在饮用水中给予DEN 8周诱导雄性白化大鼠发生肝癌，然后用NE（100mg/kg）治疗直至实验结束。大鼠接受2Gy×4的分次剂量照射。
与母体提取物和标准阿霉素相比，NE对HepG2细胞系具有显著的细胞毒性。此外，给予NE和/或γ射线照射（IRR）显著降低了肝癌诱导大鼠中升高的丙氨酸转氨酶（ALT）、总蛋白和白蛋白水平。同样，肝癌大鼠中的肿瘤标志物甲胎蛋白（AFP）和γ-谷氨酰转移酶（GGT）水平也大幅降低。此外，IRR前给予NE显著降低了聚ADP核糖聚合酶-1（PARP1）酶和Ki67的表达。此外，组织学研究有力地证实了NE和IRR联合对抗DEN诱导的肝癌的效果。
提取物的NE可能具有新的放射增敏作用，并为临床实践中对抗HCC提供新策略。
