转录组分析揭示荷叶离褶伞菌多糖LDS-1抗小鼠S180肿瘤的分子机制

以荷叶离褶伞菌多糖LDS-1、甘露聚糖肽和空白对照作用下的小鼠S180肿瘤细胞为研究材料,运用RNA-Seq测序技术进行生物信息学分析,结果显示LDS-1组、甘露聚糖肽组和空白对照组分别获得8.27、 8.35和8.97 G的分析数据.高表达基因(FPKM>2 200)分析显示LDS-1主要通过下调Rplp1基因调控细胞分裂,将S180细胞停滞在G1期以抑制其分裂.差异基因分析结果显示LDS-1主要通过上调Alb、 Timp4、 Apoa1基因调节蛋白表达或者细胞黏连性,抑制S180肿瘤细胞迁移.KEGG(京都基因与基因组百科全书)通路富集结果显示, LDS-1抑制S180肿瘤生长的关键基因主要富集在过氧化物酶体增殖物激活受体(PPAR)信号通路中,上游Fabp3基因下调,激活下游Apoa1、Slc27a2和Adipoq等多个基因上调,调控S180细胞的脂质代谢和胆固醇代谢. LDS-1能够通过调控高表达关键基因Rplp1,差异表达关键基因Alb、 Timp4、 Apoa1,以及PPAR信号通路抑制S180肿瘤细胞的增殖分裂、能量获取和迁移侵袭.

草黄口蘑多糖对S180荷瘤小鼠抗肿瘤活性分子机制研究

多糖作为口蘑属真菌的主要功能成分之一,具有免疫调节、抗氧化及抗肿瘤等活性。为明确草黄口蘑多糖的结构特征及其对S180荷瘤小鼠抗肿瘤活性相关分子机制,该研究以草黄口蘑子实体经热水浸提法提取的草黄口蘑多糖[Tricholoma lascivum (Fr.)Gillet polysaccharide,TLG-1]为实验材料,初步解析TLG-1结构,以S180荷瘤小鼠为模型检测体内抗肿瘤活性,并采用转录组测序技术对S180肿瘤组织总RNA进行测序分析。结果表明,TLG-1重均分子质量为13 442 Da,由木糖、甘露糖、葡萄糖和半乳糖4种单糖组成,其比例为1.57∶1.45∶2.84∶4.14。TLG-1可显著抑制荷瘤小鼠S180肿瘤的生长(P<0.01),抑瘤率为53.8%。转录组测序分析显示,TLG-1能显著上调mt-Co1、Prlr、Foxa1以及下调Pitx2、Rplp1、Eef1a1及Lgals1等基因,影响S180肿瘤细胞的代谢途径,调控细胞周期并抑制上皮间质转化过程。基因本体富集分析表明,TLG-1可激活细胞因子介导的信号通路,引发细胞免疫。京都基因与基因组百科全书富集分析显示,在Jak-STAT信号通路中的Il21、Il12rb2、Il12b、Il2ra、Il2rb、Il2rg、Il15ra和Ifng等基因显著上调,通过转换肿瘤相关巨噬细胞表型及分泌干扰素-γ等,增强小鼠抗肿瘤免疫应答。该研究结果为草黄口蘑多糖的开发和利用提供了一定的理论基础。

Unlocking epigenetics for precision treatment of Ewing’s sarcoma

Ewing’s sarcoma(EWS)is a highly aggressive malignant bone tumor primarily affecting adolescents and young adults.Despite the efficacy of chemoradiotherapy in some cases,the cure rate for patients with metastatic and recurrent disease remains low.Therefore,there is an urgent need for innovative therapeutic approaches to address the challenges associated with EWS treatment.Epigenetic regulation,a crucial factor in physiological processes,plays a significant role in controlling cell proliferation,maintaining gene integrity,and regulating transcription.Recent studies highlight the importance of abnormal epigenetic regulation in the initiation and progression of EWS.A comprehensive understanding of the intricate interactions between EWS and aberrant epigenetic regulation is essential for advancing clinical drug development.This review aims to provide a comprehensive overview of both epigenetic targets implicated in EWS,integrating various therapeutic modalities to offer innovative perspectives for the clinical diagnosis and treatment of EWS.

鸡血藤醇提物的提取及抗鼠肝癌S180活性研究

目的制备鸡血藤乙醇提取物水溶性部位,研究其体内抗肿瘤活性。方法采用乙醇索氏回流提取、水沉淀的方法制备鸡血藤乙醇提取物水溶性部位,并应用高效液相色谱法对其中的芒柄花素进行含量测定。采用S180荷瘤小鼠模型研究鸡血藤乙醇提取物水溶性部位的体内抗肿瘤活性,记录移植实体瘤抑制率,HE染色观察实体瘤组织和脾脏的病理改变,免疫组织化学法观察实体瘤组织Caspase-3蛋白表达情况。结果本提取工艺获得鸡血藤水溶性乙醇提取物生药含量:3.75 g生药/g浓缩稠膏,每克生药含56.25μg芒柄花素。鸡血藤醇提物高剂量能有效抑制荷瘤小鼠脾脏肥大及抑制实体瘤的生长,抑瘤率为44.70%(与模型对照组比较P<0.01)。病理HE结果表明模型组脾脏组织有肿瘤细胞浸润,实体瘤组织肿瘤细胞规整;鸡血藤醇提物高、中剂量组脾脏组织肿瘤细胞浸润减轻,实体瘤组织肿瘤细胞核固缩,肿瘤细胞凋亡、坏死,实体瘤组织Caspase-3蛋白表达增加。结论鸡血藤醇提物能显著抑制S180荷瘤小鼠实体瘤生长及减少肿瘤细胞转移,其机制可能与促进肿瘤细胞凋亡相关。

生物信息大分子功能的研究——酵母甘露聚糖对鼠Sarcoma-180瘤生长的抑制效应

酵母甘露聚糖(Mannan,简称Man)是能参与生物信息流影响生物体、特别是在糖基化方面起着重要调控作用的生物信息大分子。它是否能在抑制生物机体中肿瘤生长方面具有重要作用?研究结果表明:酵母甘露聚糖既能使患S-180瘤鼠的体质增强的同时又有抑制其体内所患S-180瘤生长的功效。Man抑制患鼠机体内的S-180瘤生长的功效(抑瘤率)随用量的增加而提高,当Man用量达360 mg(40 mg/Kg/d·9d)时,其抑瘤率达98.4%的最高水平,此时鼠体重增加1.66倍。Man的抑瘤功效有最佳适用量并存在性别敏感性,通常是雄性鼠的抑瘤率高于雌性鼠。Man抑制鼠S-180肿瘤生长的作用优于市售5-氟尿嘧啶的作用。

基于180s劲度模量的低温开裂指数预测

提出了一种通过材料性能测试,预测5~10年状况下沥青路面实际开裂的方法。依托开裂指数同沥青材料低温性能的关系,利用CAM模型(一种数学模型)拟合得到了5类常用沥青的180 s劲度模量值,预测并提出了PAV(压力老化)状态下各类沥青的开裂指数。通过数据分析,验证了该种模拟方式预测的准确性。借助长吉高速实地芯样开裂情况调研,验证CI值(低温开裂指数)对沥青路面实际开裂水平的预测效果。结果表明,CAM模型下得到的沥青梁180 s模量计算方法简单,数据置信度高,预测得到的SBS改性沥青开裂指数与路面实际开裂水平一致,证明了利用沥青材料性能预测路面实际抗裂能力这一方法的可行性。依据规范提法,给出了五类北方常用沥青的CI值参考区间。

双黄连可溶性粉对S180荷瘤小鼠腹腔巨噬细胞C3b和Fc受体的影响

旨在探究双黄连可溶性粉对S180荷瘤小鼠腹腔巨噬细胞表面C3b受体、Fc受体活性的影响,为扩大双黄连可溶性粉临床使用范围提供科学依据。以双黄连可溶性粉为研究材料,S180荷瘤小鼠为研究对象,YC-花环、EA-花环试验为研究手段,巨噬细胞C3b、Fc受体活性为检测指标,研究双黄连可溶性粉对S180荷瘤小鼠腹腔巨噬细胞C3b、Fc受体活性的影响。结果显示,小鼠接种S180瘤细胞,荷瘤小鼠腹腔巨噬细胞Fc、C3b受体活性不受影响,免疫抑制剂环磷酰胺具有降低C3b受体活性的作用(对Fc受体活性没有影响),连续给予4 d~14 d不同剂量的双黄连口服液,荷瘤小鼠腹腔巨噬细胞Fc、C3b受体活性增强,吞噬能力增强,作用优于或相当于黄芪多糖。研究结果为双黄连可溶性粉的临床应用研究提供了科学依据。

苦参碱联合PFC方案化疗对腹水型S180小鼠生存期及P170蛋白表达的影响

目的探讨苦参碱联合PFC方案(顺铂+5-氟尿嘧啶+环磷酰胺)化疗对腹水型S180小鼠生存期及P170蛋白表达的影响。方法选择健康昆明小鼠80只,适应性饲养1周,随机分为模型组、PFC组、5%苦参碱+PFC组、10%苦参碱+PFC组,每组20只。各组于右侧腋窝皮下注射S180细胞构建腹水型S180小鼠模型。接种7 d后,模型组予生理盐水0.2 mL/10 g体质量灌胃,其余三组予PFC方案化疗,5%苦参碱+PFC组、10%苦参碱+PFC组在PFC方案化疗同时分别予5%、10%苦参碱溶液0.2 mL/10 g体质量灌胃,每天1次。各组均干预4周。统计各组生存时间;接种移植瘤7 d开始称量体质量,之后7 d称量1次体质量,计算7 d体质量增加情况;称量完体质量后,抽取腹水,检测腹水中P170蛋白表达及S180细胞凋亡率。结果各组接种S180细胞1周肿瘤直径约为5 mm,小鼠出现精神萎靡、行动迟缓、毛发干枯蓬松。模型组第2周开始出现死亡,至第4周时全部死亡。其余各组第3周开始陆续出现死亡。与模型组比较,各药物干预组生存时间长(P均<0.01);与PFC组比较,5%苦参碱+PFC组和10%苦参碱+PFC组生存时间长(P均<0.05);与5%苦参碱+PFC组比较,10%苦参碱+PFC组生存时间长(P<0.05)。5%苦参碱+PFC组和10%苦参碱+PFC组干预2、3、4周体质量增加均高于PFC组同期,且10%苦参碱+PFC组干预2、3、4周体质量增加均高于5%苦参碱+PFC组同期(P均<0.05)。5%苦参碱+PFC组和10%苦参碱+PFC组干预3、4周腹水中P170蛋白表达均低于PFC组同期,S180细胞凋亡率均高于PFC组同期,以10%苦参碱+PFC组干预3、4周变化更明显(P均<0.05)。结论5%、10%苦参碱联合PFC方案化疗均能显著改善腹水型S180小鼠生存期,抑制腹水中P170蛋白表达,促进腹水中S180细胞凋亡,以10%苦参碱联合PFC方案化疗效果较好。

Antitumor effect and mechanism of Gecko on human esophageal carcinoma cell lines in vitro and xenografted sarcoma 180 in Kunming mice

AIM: To investigate the anti-tumor effect of Chinese medicine Gecko on human esophageal carcinoma cell lines and xenografted sarcoma 180 in Kunming mice and its mechanism. METHODS: The serum pharmacological method was used in vitro . The growth rates of the human esophageal carcinoma cells (EC9706 or EC1) were measured by a modifi ed 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The transplanted tumor model of the mouse S180 sarcoma was established. Fifty mice were randomly divided into fi ve groups (n = 10). Three Gecko groups were treated respectively with oral administration of Gecko powder at a daily dose of 13.5 g/kg, 9 g/kg, and 4.5 g/kg. The negative group (NS group) was treated with oral administration of an equal volume of saline and the positive group (CTX group) was treated with 100 mg/kg Cytoxan by intraperitoneal injection at the fi rst day. After 2 wk of treatment, the anti-tumor activity was evaluated by tumor tissue weighing. The impact on immune organ was detected based on the thymus index, spleen index, phagocytic rate and phagocytic index. The protein expression of vascular endothelingrowth factor (VEGF) and basic fibroblast growth factor (bFGF) were detected by immunohistochemistry. The cell apoptotic rate was detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay. RESULTS: The A value in each group treated with Gecko after 72 h was reduced signif icantly in EC9706 and in EC1. The tumor weight in each group of Gecko was decreased signifi cantly (1.087 ± 0.249 vs 2.167 ± 0.592; 1.021 ± 0.288 vs 2.167 ± 0.592; 1.234 ± 0.331 vs 2.167 ± 0.592; P < 0.01, respectively). However, the thymus index and Spleen index of mice in Gecko groups had no significant difference compared with the NS group. The immunoreactive score of VEGF and bFGF protein expression of each Gecko group by immunohistochemical staining were lowered signifi cantly. The apoptosis index (AI) of each group was increased progressively with increase of dose of Gecko by TUNEL. CONCLUSION: Gecko has anti-tumor effects in vitro and in vivo; induction of tumor cell apoptosis and the down-regulation of protein expression of VEGF and bFGF may be contributed to anti-tumor effects of Gecko.

Anticancer effect of Jinlongshe granules on in situ-transplanted human MKN-45 gastric cancer in nude mice and xenografted sarcoma 180 in Kunming mice and its mechanism

AIM： To study the antitumor effect of Chinese compound Jinlongshe （JLS） granules on sarcoma 180 and MKN-45 human gastric cancer cell lines in vivo and its mechanism. METHODS： After establishment of S180 sarcoma （S180） and MKN-45 gastric cancer model of nude mice, the tumor-bearing mice were divided into 5 groups at random. Three experimental groups were respectively given the aqueous extract of JLS granules at doses of 120 g, 60 g and 20 g/（kg per 6/wk,i.g） for 3 wk in S180 and 6 wk in nude mice model. Positive control was given cyclophosphamide （Cy） at a dose of 50 mg/（kg per 3/wk, i.g） for 3 wk in S180 models and 5-Fluorouracil （5-FU） 20 mg/（kg per 3/wk, i.g） for 3 wk in nude mice model. Negative control was given normal saline （NS） at a dose of 0.18 g/（kg per 6/wk, i.g） respectively. After 3 wk in mice bearing S180 tumor and 6 wk in nude mice model, the experimental animals were sacrificed and the masses of tumor were weighed, and the rates of tumor inhibition of each treated group were calculated respectively. To determine the antitumor mechanisms, the morphological changes, cell cycle and apoptosis were observed in MKN-45 nude mice model. Annexin V-FITC/PI double staining FCM assay was used to further determine the live cells, apoptotic cells, necrotic cells and debris. RESULTS： The inhibitory rates of JLS granules at the doses of 20 g/kg, 60 g/kg and 120 g/kg were 50.31%, 55.94% and 68.13% （P 〈 0.01） in nude mice models and 40.90%, 50.32% and 58.46% （P 〈 0.01） in S180 model. The inhibitory rate of Cy was 85.22% in S180 models and the inhibitory rate of 5-FU was 53.43% in nude mice model （P 〈 0.01）. Nuclear chromatin and margination were observed under a transmission electron microscope （TEM）. The G0/G1 phase was arrested, typical apoptotic peak appeared, the apoptotic rate was 22.81%-38.54% in three JLS granule-treated groups. Annexin V-FITC/PI double staining FCM assay showed that the apoptotic cells were 4.36%, 3.08% and 7.08% in three dosages, most cells were localized in the low right quadrant. CONCLUSION：Jinlongshe granules possess anti-tumor effects on experimental tumor models in vivo, and apoptosis induction is one of its anti-tumor mechanisms.

美洲大蠊提取物CⅡ-3对荷S180肉瘤小鼠抑瘤作用及机制初探

目的:探讨美洲大蠊提取物CⅡ-3对荷S180肉瘤小鼠抑瘤作用及机制。方法:将荷S180肉瘤小鼠随机分为模型组、阳性对照(CTX)组、CⅡ-3高、中、低剂量组,另设正常对照组,每组10只小鼠,观察给药后各组小鼠肿瘤组织的病理改变,计算抑瘤率;ELISA试剂盒检测血清中血管内皮生长因子(VEGF)和端粒酶(TE)水平;免疫组织化学法检测肿瘤组织中p53、B细胞淋巴瘤-2(Bcl-2)、含半胱氨酸的天冬氨酸蛋白水解酶-3(Caspase-3)、微血管密度(MVD)和环氧合酶-2(COX-2)蛋白的表达。结果:CTX组、CⅡ-3高、中、低剂量组小鼠抑瘤率分别为85.71%、55.71%、44.28%、34.28%。CⅡ-3高、中剂量组小鼠肿瘤组织坏死区域明显。与模型组相比,CⅡ-3高剂量组小鼠血清中TE活力降低(P<0.05),CⅡ-3高、中剂量组小鼠肿瘤组织中p53、Bcl-2、MVD、COX-2表达显著降低(P<0.01),Caspase-3表达显著增加(P<0.01)。结论:CⅡ-3能显著抑制S180肉瘤的生长,其机制可能与降低TE活力,减少肿瘤组织中p53、Bcl-2、MVD、COX-2表达,增加Caspase-3表达等途径相关。

AUGMENTATION OF IMMUNE FUNCTIONS AND AUTOLOGOUS TUMOR-KILLING ACTIVITY BY KAPPA-SELENOCARRAGEENAN IN MICE BEARING SARCOMA 180

Objective: To study the enhancement of the immune functions and autologous tumor killing (ATK) activity by kappa selenocarrageenan (KSC) in mice bearing sarcoma 180. Methods: To measure the effects of KSC and/or Cyclophosphamide (Cy) on natural killer (NK) activity, lymphokine activated killer (LAK) activity, the produc tion of interleukin 2 (IL 2), ATK activity and the growth of sarcoma 180 (S 180 ). Results: KSC promoted NK activity, LAK activity and ATK activity in vivo , increased IL 2 production at 40 mg/kg/d×9d. It also enhanced the antitumor action of Cy (20 mg/kg/d×9d) and offset the inhibition of Cy on immunocopetent cells. The ATK activity in splenocytes of S 180 bearing mice could be induced and increased by recombinant interleukin 2 (rIL 2) in vitro . Conclusion: KSC has an up regulating effect on the immune functions and ATK activity in tumor bearing mice. It can be used as a biological response modifier (BRM) in cancer biotherapy.

Extraskeletal Ewing sarcoma of the stomach:A rare case report

BACKGROUND Extraskeletal Ewing sarcoma(EES)is a rare and highly malignant small round cell tumor associated with a poor clinical outcome.Ewing sarcoma(ES)involving the stomach is an uncommon presentation and can be easily confused with other small round cell tumors.We herein present a rare case of ES involving the gastric area.CASE SUMMARY We report a case of gastric ES in a 19-year-old female patient who initially presented with a complaint of a tender epigastric mass for 5 d.Contrast-enhanced abdominal computed tomography revealed a soft-tissue-density mass with a diameter of 8.5 cm between the liver and stomach;the mass was connected to the gastric antrum.Then,the mass was surgically excised completely.Upon histopathological,immunophenotype and molecular analysis,the mass was identified to be a primary gastric ES.CONCLUSION EES is an aggressive tumor with poor prognosis.Therefore,early diagnosis and timely intervention are essential for a good prognosis.It is imperative for us to raise awareness about this rare tumor.Surgical resection is still the best treatment option.

Modulation of MMP-2 and TIMP-2 by low dose radiation in mice bearing S180 sarcoma

Objective To investigate the inhibition of low dose radiation （LDR） on S180 sarcomas and its modulation of MMP-2 and TIMP-2 in mice. Methods $180 subcutaneously implanted tumor model mice were randomly divided into two groups： control （N） and low dose radiation （LDR） groups. N mice were sacrificed after 12 h, whereas LDR mice were sacrificed after 12 （LDR-12 h）, 24 （LDR-24 h）, 48 （LDR-48 h）, and 72 （LDR-72 h） h. Thereafter, we measured the tumor volumes. Histopathology was performed, and P-V immunohistochemistry was applied to assess MMP-2 and TIMP-2 expression. Results Compared with the control group, the tumor growth was significantly inhibited in the LDR groups （P 〈 0.05）. MMP-2 expression was considerably reduced in LDR-24h （P 〈 0.05） and LDR-48h （P 〈 0.05）, whereas the change of TIMP-2 was not obvious in the LDR groups （P 〉 0.05） in contrast to that of the control group. Conclusion LDR can effectively suppress the growth of S180 implanted tumors by reducing MMP-2, which is associated with invasion and metastasis.

Effect of hyperthermia in combination with cryotherapy on sarcoma 180 in mice

The significant decrease in tumor recurrence caused by combined hyperthermia (local water bath) with cryotherapy has previously been shown. This study demonstrated an in vivo additive interaction of local microwave diathermy (hyperthermia, 42±0.5℃, 20 min. ) and liquid nitrogen treatment (cryotherapy,-180℃, 3 min. ) against intraperitoneally implanted sarcoma 180 in ICR mice. Local hyperthermia was produced by applicating 2450 MHz microwave to the region of the tumor without induction of significant whole body hyperthermia.Both hyperthermia and cryotherapy were delivered as a single dose individually on day 1 and day 2. The analysis of the tumor size curves showed that all of the treatments had more significant effect on sarcoma 180 than on the control group (P < 0. 0001 ). The optimal sequence of the combined therapies found in the experiment was cryotherapy→hyperthermia (CH) (P<0. 0001). Weights of the tumors excised from the mice on day 11 showed that the combined therapies (cryotherapy→hyperthermia or hyperthermia→cryotherapy) were more effective on sarcoma 180 than hyperthermia or cryotherapy used alone(P<0.01).

Fruiting increases total content of flavonoids and antiproliferative effects of Cereus jamacaru D.C. cladodes in sarcoma 180 cells in vitro

Objective: To evaluate the influence of fruiting phenological stage on total flavonoid content, antioxidant activity, and antiproliferative effects of Cereus jamacaru(C. jamacaru)(mandacaru) cladodes and fruit. Methods: Fruit and cladodes at vegetative and fruiting stage of C. jamacaru were collected. The fruit was dissected and bark, pulp, and seeds were separated. Vegetative and fruiting cladodes, together with bark, pulp, and seeds were used to obtain five hydroalcoholic extracts. The extracts were investigated for total flavonoid content, using AlCl3 colorimetric method, antioxidant activity by 2,2-diphenyl-1-picrylhydrazyl and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radical scavenging capacity and Fe^(2+) ion chelating activity, and in vitro antiproliferative effects(sarcoma 180 cells) by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2 H-tetrazolium bromide assay. Results: The extract of C. jamacaru cladodes at the fruiting stage showed higher flavonoid content compared to the other extracts. Seed extracts showed the highest antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) assays, and the extract of cladodes at vegetative stage showed better antioxidant activity in Fe^(2+) ion chelating activity. The extract of fruiting cladodes promoted higher antiproliferative effects compared to the other extracts. Conclusions: These findings suggest that fruiting increases the content of flavonoids and antiproliferative effects of C. jamacaru cladodes. Data reinforce the potential use of C. jamacaru cladodes and fruits as natural antioxidants and potent anticancer agent.

EFFECTS OF GALLIUM AND ITS COMBINATION WITH SELENIUM ON MOUSE S_180 SARCOMA AND BONE GALLIUM CONTENT

Kunming female mice were used and S180 sarcoma cells were transplanted subeutaneously into right anterior armpit or the mice. The mice were divided into three groups randomly, and orally administered with water, gallium chloride and GaCl3+ Na2SeO3 respectively for 2 weeks. After that,the tumors and foreleg bones were taken out for study. The experimental results showed that oral administration with gallium chloride-could inhibit the growth or S180 sarcoma in mice and the tumor morphology was changed. Selenium could accelerate the gallium entering into bone. This fact might supply a new clue to further clinical application of gallium and selenium.

The effect of low-dose total body irradiation on tumor-inhibition and signal transduction in tumor tissues of mice bearing S180 sarcoma

Objective： By studying the influence of low-dose total body irradiation to proliferating cell nuclear antigens （PCNA）, epidermal growth factor receptor （EGFR）, erythropoietin （EPO） and vascular endothelial growth factor receptor （VEGFR） of tumor tissues in mice bearing S180 sarcoma, to further explore the mechanism of low doses radiation. Methods：S180 sarcoma cells were implanted subcutaneously into 58 male Kunming mice. Randomly these mice were divided into sham-irradiation （S） group and low-dose radiation （LDR） group. 12 days after implantation, the mice in LDR group were once delivered 75 mGy total-body ^60Co y-ray irradiation, while the mice in S group were left without irradiation. Then the mice in LDR group were executed at 6 h （LDR-6h group）, 12 h （LDR-12 h group）, 24 h （LDR-24 h group）, 48 h （LDR-48 h group） and 72 h （LDR-72h group） after irradiation. Tumor tissues were weighed and histological observed. Immunohistochemical staining was used to detect the expression of PCNA, VEGF, EPO and VEGFR of tumor tissues. Results： Though there was no significant difference between LDR group and S group in tumor weight, after irradiation the expression of PCNA and EPO of tumor tissues in LDR group decreased with time. LDR-24h, LDR-48h and LDR-72h groups were all statistically significantly different from S group. The expression of EGFR and VEGFR also decreased, and LDR-24h group was the lowest （P 〈 0.05）. Conclusion： Seventy-two h after low-dose total body irradiation, there was no significant change in tumor size of mice bearing S180 sarcoma. Low-dose total body radiation decreased the expression of PCNA inhibiting tumor growth; reduced the expression of EGFR in tumor tissue impacting the signal transduction of tumor cells. The study also indicated that low-dose total body irradiation, within a certain period of time, can decrease the expression of hypoxia factor EPO and VEGFR, which may improve the situation of tumor hypoxia and radiosensitivity of tumor itself.

Saponin from Tupistra chinensis Bak Inhibits NF-κB Signaling in Sarcoma S-180 Cell Mouse Xenografts

This study examined the effect of saponins from Tupistra chinensis Bak （STCB） on the growth of sarcoma S-180 cells in vitro and in mouse xenografts as well as the underlying mechanisms. Cell proliferation was assessed by MTT assay. Cell cycle distribution was determined by flow cytometry. Sarcoma S-180 tumor-bearing mice were treated with different doses of STCB with 10 μg/mL 5-fluorouracil （5-Fu） as a positive control. The activity of nuclear factor （NF）-κB was detected by gel mobility shift assay. The mRNA level of NF-κB was determined by real-time quantitative RT-PCR. The results showed that in vitro STCB inhibited the growth of S-180 cells in a concentration-dependent manner, which was accompanied by cell cycle arrest at S-phase. In vivo STCB significantly inhibited the growth of S-180 tumor mouse xenografts in a dose-dependent manner with apparent induction of cell apoptosis. Moreover, STCB inhibited the activity of NF-rd3 p65 and reduced the expression of NF-κB p65 mRNA in mouse xenografts. It was concluded that STCB inhibits the proliferation and cell cycle progression of S- 180 cells by suppressing NF-κB signaling in mouse xenografts. Our findings suggest STCB is a promising agent for the treatment of sarcoma.