Ghorbani Alvanegh Akbar, Mirzaei Nodooshan Majid, Dorostkar Ruhollah, Ranjbar Reza, Jalali Kondori Bahman, Shahriary Alireza, Parastouei Karim, Vazifedust Soheil, Afrasiab Elmira, Esmaeili Gouvarchinghaleh Hadi
Human Genetics Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Applied Virology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Infect Agent Cancer. 2023 Jul 31;18(1):46. doi: 10.1186/s13027-023-00521-y.
Colorectal Cancer (CRC) is a frequent malignancy with a high mortality rate. Specific inherited and environmental influences can affect CRC. Oncolytic viruses and bacteria in treating CRC are one of the innovative therapeutic options. This study aims to determine whether mesenchymal stem cells (MSCs) infected with the Newcastle Disease Virus (NDV) in combination with Lactobacillus casei extract (L. casei) have a synergistic effects on CRC cell line growth.
MSCs taken from the bone marrow of BALB/c mice and were infected with the 20 MOI of NDV. Then, using the CT26 cell line in various groups as a single and combined treatment, the anticancer potential of MSCs containing the NDV and L. casei extract was examined. The evaluations considered the CT26 survival and the rate at which LDH, ROS, and levels of caspases eight and nine were produced following various treatments.
NDV, MSCs-NDV, and L. casei in alone or combined treatment significantly increased apoptosis percent, LDH, and ROS production compared with the control group (P˂0.05). Also, NDV, in free or capsulated in MSCs, had anticancer effects, but in capsulated form, it had a delay compared with free NDV. The findings proved that L. casei primarily stimulates the extrinsic pathway, while NDV therapy promotes apoptosis through the activation of both intrinsic and extrinsic apoptosis pathways.
The results suggest that MSCs carrying oncolytic NDV in combination with L. casei extract as a potentially effective strategy for cancer immunotherapy by promoting the generation of LDH, ROS, and apoptosis in the microenvironment of the CT26 cell line.
结直肠癌(CRC)是一种常见的恶性肿瘤,死亡率很高。特定的遗传和环境因素会影响结直肠癌。溶瘤病毒和细菌在治疗结直肠癌方面是创新的治疗选择之一。本研究旨在确定感染新城疫病毒(NDV)的间充质干细胞(MSCs)与干酪乳杆菌提取物(干酪乳杆菌)联合使用是否对结直肠癌细胞系生长具有协同作用。
从BALB/c小鼠骨髓中获取间充质干细胞,并感染20 MOI的新城疫病毒。然后,以CT26细胞系作为各个组的单一治疗和联合治疗对象,检测含有新城疫病毒和干酪乳杆菌提取物的间充质干细胞的抗癌潜力。评估内容包括各种处理后CT26细胞的存活率以及乳酸脱氢酶(LDH)、活性氧(ROS)的产生速率,还有半胱天冬酶8和9的水平。
与对照组相比,单独或联合处理的新城疫病毒、感染新城疫病毒的间充质干细胞和干酪乳杆菌均显著增加了凋亡百分比、LDH和ROS的产生(P˂0.05)。此外,游离或包裹在间充质干细胞中的新城疫病毒均具有抗癌作用,但包裹形式的与游离新城疫病毒相比作用有所延迟。研究结果证明,干酪乳杆菌主要刺激外源性途径,而新城疫病毒疗法通过激活内源性和外源性凋亡途径促进细胞凋亡。
结果表明,携带溶瘤新城疫病毒的间充质干细胞与干酪乳杆菌提取物联合使用,通过促进CT26细胞系微环境中LDH、ROS的生成和细胞凋亡,是一种潜在有效的癌症免疫治疗策略。