Liaoning Laboratory of Cancer Genetics and Epigenetics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, 116044, China.
South China University of Technology School of Medicine, Guangzhou, 520006, China.
BMC Cancer. 2018 Sep 3;18(1):871. doi: 10.1186/s12885-018-4771-1.
Although our previous study revealed lumbar punctured resveratrol could remarkably prolong the survival of rats bearing orthotopic glioblastomas, it also suggested the administration did not completely suppress rapid tumour growth. These evidences led us to consider that the prognosis of tumour-bearing rats may be further improved if this treatment is used in combination with neurosurgery. Therefore, we investigated the effectiveness of the combined treatment on rat orthotopic glioblastomas.
Rat RG2 glioblastoma cells were inoculated into the brains of 36 rats. The rats were subjected to partial tumour removal after they showed symptoms of intracranial hypertension. There were 28 rats that survived the surgery, and these animals were randomly and equally divided into the control group without postoperative treatment and the LP group treated with 100 μl of 300 μM resveratrol via the LP route. Resveratrol was administered 24 h after tumour resection in 3-day intervals, and the animals received 7 treatments. The intracranial tumour sizes, average life span, cell apoptosis and STAT3 signalling were evaluated by multiple experimental approaches in the tumour tissues harvested from both groups.
The results showed that 5 of the 14 (35.7%) rats in the LP group remained alive over 60 days without any sign of recurrence. The remaining nine animals had a longer mean postoperative survival time (11.0 ± 2.9 days) than that of the (7.3 + 1.3 days; p < 0.05) control group. The resveratrol-treated tumour tissues showed less Ki67 labelling, widely distributed apoptotic regions, upregulated PIAS3 expression and reduced p-STAT3 nuclear translocation.
This study demonstrates that postoperative resveratrol administration efficiently improves the prognosis of rat advanced orthotopic glioblastoma via inhibition of growth, induction of apoptosis and inactivation of STAT3 signalling. Therefore, this therapeutic approach could be of potential practical value in the management of glioblastomas.
虽然我们之前的研究表明，腰椎穿刺白藜芦醇可以显著延长原位脑胶质瘤大鼠的存活时间，但也表明该治疗方法并不能完全抑制肿瘤的快速生长。这些证据促使我们考虑，如果将这种治疗方法与神经外科手术结合使用，肿瘤荷瘤大鼠的预后可能会进一步改善。因此，我们研究了联合治疗对大鼠原位脑胶质瘤的疗效。
将大鼠 RG2 脑胶质瘤细胞接种到 36 只大鼠的大脑中。当这些大鼠出现颅内压升高的症状时，对其进行部分肿瘤切除。有 28 只大鼠在手术后存活下来，这些动物被随机平均分为对照组（无术后治疗）和 LP 组（通过 LP 途径给予 100μl 300μM 白藜芦醇）。在肿瘤切除后 24 小时，以 3 天为间隔，用白藜芦醇进行治疗，动物共接受 7 次治疗。通过对两组肿瘤组织进行多种实验方法评估颅内肿瘤大小、平均寿命、细胞凋亡和 STAT3 信号转导。
结果显示，LP 组中有 5 只（35.7%）大鼠在没有任何复发迹象的情况下存活超过 60 天。其余 9 只动物的术后平均存活时间（11.0±2.9 天）长于对照组（7.3±1.3 天；p<0.05）。用白藜芦醇处理的肿瘤组织 Ki67 标记较少，广泛分布的凋亡区域，PIAS3 表达上调，p-STAT3 核转位减少。
本研究表明，术后给予白藜芦醇可通过抑制生长、诱导凋亡和失活 STAT3 信号转导，有效改善大鼠晚期原位脑胶质瘤的预后。因此，这种治疗方法在治疗脑胶质瘤方面具有潜在的实用价值。
