Inhibition Effects of Alantolactone on the Proliferation of Human Osteosarcoma cells
WANG Xiao-dong1,2,3, LI Xin2,4, TONG Xiao-qiong2, YU Chun-lei2, YUAN Bin2
1. Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong 637000, China; 2. School of Pharmacy, North Sichuan Medical College, Institute of Materia Medica, Nanchong 637000, China; 3. Nanchong City Key Laboratory of Personalized Drug Treatment, Nanchong 637000, China; 4. School of Nursing Affiliated Hospital, North Sichuan Medical College, Nanchong 637000, China
Abstract：OBJECTIVE To investigate the inhibitory effect of alantolactone(ALT) on the proliferation of 143B and saos-2 cells of osteosarcoma cells. METHODS The proliferation and vitality effect of ALT on 143B and saos-2 cells were evaluated by CCK-8 and EdU assay. The invasion and migration effect of ALT on 143B and saos-2 cells were detected by cell invasion and cell scratch method. The effects of ALT on the cell cycle and apoptosis of 143B and saos-2 cells were detected by flow cytometry. The effects of ALT on LAT1, SKA2, BUB1B, BCL2 and STAT3 mRNA and protein levels in 143B and saos-2 cells were measured by qPCR and WB. RESULTS ALT could significantly inhibit the proliferation, migration and invasion of 143B and saos-2 cells. ALT could block cells at G1 phase, and induce the apoptosis of 143B and saos-2 cells(P<0.05 or P<0.01). Compared with the control group, the expressions of LAT1mRNA and protein, SKA2 and BUB1BmRNA and protein, BCL2 and STAT3mRNA and protein in 143B and saos-2 cells were all decreased by ALT, and the difference was statistically significant(P<0.05 or P<0.01). CONCLUSION ALT can inhibit the proliferation, migration and invasion of osteosarcoma 143B and saos-2 cells, and induce apoptosis and arrest the cell cycle of 143B and saos-2 in G1 phase, and its mechanism may be related to multiple links such as inhibiting amino-acid transport(LAT1),regulating cell cycle(SKA2,BUB1B), and promoting cell apoptosis(STAT3,BCL2).
王晓冬, 李鑫, 童晓琼, 于春雷, 袁斌. 土木香内酯抑制骨肉瘤细胞生长作用研究[J]. 中国药学杂志, 2023, 58(2): 151-159.
WANG Xiao-dong, LI Xin, TONG Xiao-qiong, YU Chun-lei, YUAN Bin. Inhibition Effects of Alantolactone on the Proliferation of Human Osteosarcoma cells. Chinese Pharmaceutical Journal, 2023, 58(2): 151-159.
GLOVER J, MAN T K, BARKAUSKAS D A, et al. Osteosarcoma enters a post genomic era with in silico opportunities:generation of the High Dimensional Database for facilitating sarcoma biology research:a report from the Children's Oncology Group and the QuadW Foundation[J]. PLoS One, 2017, 12(7):e0181204. Doi:10.1371/journal.pone.0181204.
[2]
KANG X Z, HUANG Z, SHI A H, et al. Deficiencies in the diagnosis and treatment of pulmonary metastatic osteosarcoma: a Chinese multidisciplinary survey[J]. Chin J Lung Cancer(中国肺癌杂志), 2016, 19(3): 153-160.
[3]
MICHAEL S I, STEFAN S B, PAUL M, et al. Osteosarcoma:current treatment and a collaborative pathway to success[J]. J Clin Oncol, 2015, 33(27): 3029-3035.
[4]
MA N, KANG Y, CUI Y X, et al. Inhibitory effects of TPD7 on migration and invasion of breast cancer cells[J]. J Mod Oncol (现代肿瘤医学), 2019, 27(5):728-733.
[5]
WANG X, WANG L T, ZHANG B. Effect of alantolactone on migration, invasion and apoptosis in glioma C6 cells[J]. Acta Lab Anim Sci Sin (中国实验动物学报), 2018, 26(3):317-322.
[6]
XIE L X, XU Q Q, XU H X, et al. Inhibitory effect and mechanism of Alantolactone in cervix cancer cells[J]. J Pract Med (实用医学杂志), 2020, 36(3):288-293.
[7]
SOMMER P, LE ROUZIC P, GILLINGHAM H, et al. Glucocorticoid receptor overexpression exerts an antisurvival effect on human small cell lung cancer cells[J]. Oncogene, 2007, 26(50):7111-7121.
[8]
SHI C, LAN W J, WANG Z K, et al. Alantolactone inhibits cell autophagy and promotes apoptosis via AP2M1 in acute lymphoblastic leukemia[J]. Cancer Cell Int, 2020, 20:442.Doi:10.1186/s12935-020-01537-9.
[9]
ZHANG Y, WENG Q, HAN J, et al. Alantolactone suppresses human osteosarcoma through the PI3K/AKT signaling pathway[J]. Mol Med Rep, 2020, 21(2):675-684.
[10]
HAN J. Inhibitory effect of 12- epi-Owuline on leukemia and its mechanism[D]:Nanchong:North Sichuan Medical College(川北医学院), 2020.
[11]
HE Y, CAO X, KONG Y, et al. Apoptosis-promoting and migration-suppressing effect of alantolactone on gastric cancer cell lines BGC-823 and SGC-7901 via regulating p38MAPK and NF-kappaB pathways[J]. Hum Exp Toxicol, 2019, 38(10):1132-1144.
[12]
WANG Y T. Expression and function analysis of PRR11-Ska2 "gene pair" in lung cancer[D]. Chongqing:Chongqing Medical University (重庆医科大学), 2014.
[13]
WANG F L. Inhibition of proliferation and apoptosis of smmc-7721 cells induced by Muc1 gene silencing[D]. Changchun: Jilin University (吉林大学), 2013.
[14]
RICE L, WATERS C E, ECCLES J, et al. Identification and functional analysis of SKA2 interaction with the glucocorticoid receptor[J]. J Endocrinol, 2008, 198(3):499-509.
[15]
YANG C M, ZHANG L L, HUANG H K, et al. Effect of alantolactone on malignant biological behaviors of human osteosarcoma 143B cells[J]. Chin J Cancer Biother (中国肿瘤生物治疗杂志), 2020, 27(4):377-384.
[16]
QIN S J, LIU Q Y, TANG Z N, et al. Molecular mechanism of miR-509-3 p regulating the proliferation, inva-sion, migration and apoptosis of breast cancer cells by targeting BCL2 gene[J]. Chin J Gerontol (中国老年学杂志), 2019, 39(23):5769-5774.
[17]
WANG D, SUO Y J, GONG L, et al. SKA2 promotes proliferation and invasion of hepatocellular carcinoma cells via activating the beta-catenin signaling pathway[J]. Neoplasma, 2020, 67(4):743-750.
[18]
IJABI J, AFRISHAM R, MORADI-SARDAREH H, et al. The shift of HbF to HbA under influence of SKA2 gene; A possible link between cortisol and hematopoietic maturation in term and preterm newborns[J]. Endocr Metab Immune Disord Drug Targets, 2021, 21(3):485-494.
[19]
QU Y Z, ZHAO Y L, GAO G D, et al. Study on the effects of erigeron injection in prevention and treatment of cerebral ischemia and reperfusion injury[J]. Med J Natl Defending Forces Northwest China (西北国防医学杂志), 2002, 23(2):124-125.
[20]
WANG L N, LIU F, ZHANG W L, et al. Effect of ganglioside on bcl - 2 mRNA expression in experimental acute spinal cord injury rats[J]. Chin J Crit Care Med(中国急救医学), 2006, 26(9):680-681.
[21]
LUCANTONI F, SALVUCCI M, DUSSMANN H, et al. BCL(X)L and BCL2 increase the metabolic fitness of breast cancer cells:a single-cell imaging study[J]. Cell Death Differ, 2020, 28(5): 1512-1531.
[22]
CUI Y, SU Y, DENG L Y, et al. Ginsenoside-Rg5 inhibits retinoblastoma proliferation and induces apoptosis through suppressing BCL2 expression[J]. Chemotherapy, 2018, 63(5):293-300.
[23]
ZHANG B L, MA L G, YIN W L, et al. Effect of intervention of bcl-2 gene expression on invasion and migration ability of osteosarcoma cells[J]. Chin J Gerontol (中国老年学杂志), 2018, 38(12):2975-2977.
[24]
DU H H. Effects and mechanisms of Toxoplasma gondii exosomes on proliferation inhibition and induction of apoptosis of lung cancer cells[D]. Jinan:Shandong University(山东大学), 2020.
[25]
EL ANSARI R, CRAZE M L, MILIGY I, et al. The amino acid transporter SLC7A5 confers a poor prognosis in the highly proliferative breast cancer subtypes and is a key therapeutic target in luminal B tumours[J]. Breast Cancer Res, 2018, 20(1): 21. Doi:10.1186/s13058-018-0946-6.
[26]
WU F Y. Study on the protective effect of anisodamine on endothelial cells induced by 5-fluorouracil and the underlying mechanisms[D]. Nanning:Guangxi Medical University(广西医科大学), 2017.
[27]
MASAHIKO K, MARYAM K, NAOHIKO A, et al. Properties of L-Type amino acid transporter 1 in epidermal ovarian cancer[J]. Int J Gynecol Cancer, 2010, 20(3): 329-336.
2023, Vol. 58 
