Effect of Olaparib on Ovarian Cancer SKOV3 Cell Line Proliferation by Inhibiting the PI3K/AKT/mTOR Signaling Pathway
MA Yan-ying1, YUAN Bo2, ZHAO Wen-bo3*, ZHAO Dong-mei1
1. Department of Pathology, the Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450003, China; 2. Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, China; 3. College of Chemistry and Chemical Engineering, Zhengzhou Normal University, Zhengzhou 450044, China
Abstract��OBJECTIVE To analyze the involvement of PI3K/AKT/mTOR signaling pathway on the inhibiting the proliferation of ovarian cancer SKOV3 cell line by olaparib. METHODS The SKOV3 cells were randomly divided into five groups: control group, olaparib low dose group (10 mg��L-1), olaparib medium dose group (30 mg��L-1), olaparib high dose group (90 mg��L-1), and PI3K protein inhibitor LY294002 group (10 mg��L-1). In addition to the control group, the rest of the cells were incubated with the corresponding doses of the compounds. DAPI and Western blotting were used to analyze the expression of apoptotic protein. qPCR, Western blotting and immunocytochemistry were adopted to detect the expression of PI3K/AKT/mTOR signaling pathway related proteins. RESULTS After olaparib treatment, the proliferation of ovarian cancer SKOV3 cells was significantly inhibited (P<0.05). Apoptotic bodies in SKOV3 cells increased gradually, and the expression of caspase 3 and caspase 9 increased gradually (P<0.05), PI3K, AKT and mTOR expression gradually decreased (P<0.05) after olaparib medication. With the increase of olaparib level, the above effects were more obvious (P<0.05). CONCLUSION Olaparib has an inhibitory effect on ovarian cancer SKOV3 cells, and it may play a role by inhibiting the PI3K/AKT/mTOR signaling pathway.
����Ӣ, Ԭ��, ���IJ�, �Զ�÷. ����������ѳ���SKOV3ϸ��PI3K/AKT/mTOR�ź�ͨ·��Ӱ��[J]. �й�ҩѧ��־, 2019, 54(1): 36-41.
MA Yan-ying, YUAN Bo, ZHAO Wen-bo, ZHAO Dong-mei. Effect of Olaparib on Ovarian Cancer SKOV3 Cell Line Proliferation by Inhibiting the PI3K/AKT/mTOR Signaling Pathway. Chinese Pharmaceutical Journal, 2019, 54(1): 36-41.
COPUR M S, GAUCHAN D, RAMAEKERS R, et al. Neoadjuvant chemotherapy or primary debulking surgery for stage iiic ovarian cancer[J]. J Clin Oncol, 2017, 35(7):802-803.
[2]
HUANG L, JIN Y, FENG S, et al. Role of wnt/beta-catenin, wnt/c-jun n-terminal kinase and wnt/Ca2+ pathways in cisplatin-induced chemoresistance in ovarian cancer[J]. Exp Ther Med, 2016, 12(6):3851-3858.
[3]
HUANG R Y, ANTONY J, TAN T Z, et al. Targeting the axl signaling pathway in ovarian cancer[J]. Mol Cell Oncol, 2017, 4(2):e1263716.
[4]
LIU X, FENG M, ZHENG G, et al. Tcrp1 expression is associated with platinum sensitivity in human lung and ovarian cancer cells[J]. Oncol Lett, 2017, 13(3):1398-1405.
[5]
LU J, XU Y, WEI X, et al. Emodin inhibits the epithelial to mesenchymal transition of epithelial ovarian cancer cells via ilk/gsk-3beta/slug signaling pathway[J]. Biomed Res Int, 2016, 20166253280.
[6]
CHEAIB B, AUGUSTE A, LEARY A. The pi3k/akt/mtor pathway in ovarian cancer: therapeutic opportunities and challenges[J]. Chin J Cancer(��֢), 2015, 34(1):4-16.
[7]
YU P, YE L, WANG H, et al. Nsk-01105 inhibits proliferation and induces apoptosis of prostate cancer cells by blocking the raf/mek/erk and pi3k/akt/mtor signal pathways[J]. Tumour Biol, 2015, 36(3):2143-2153.
[8]
PUJADE-LAURAINE E, COMBE P. Olaparib in ovarian cancer with brca mutation [J]. Bull Cancer, 2015, 102(6 suppl 1):S82-84.
[9]
TEWARI K S, ESKANDER R N, MONK B J. Development of olaparib for brca-deficient recurrent epithelial ovarian cancer[J]. Clin Cancer Res, 2015, 21(17):3829-3835.
[10]
JIANG C M H Z, YANG Q. Effect of apoptosis inducing of ginsenoside compound k on chronic myelocytic leukemia k562 cells and its mechanism[J]. J Chin Oncol(����ѧ��־), 2014, 20(2):122-126.
[11]
VAN DER STEEN S C, RAAVE R, LANGERAK S, et al. Targeting the extracellular matrix of ovarian cancer using functionalized, drug loaded lyophilisomes[J]. Eur J Pharm Biopharm, 2017, 113229-239.
[12]
ZHANG S, NG M K. Gene-microrna network module analysis for ovarian cancer[J]. BMC Syst Biol, 2016, 10(suppl 4):117.
[13]
BAI X, MA Y, ZHANG G. Butein suppresses cervical cancer growth through the pi3k/akt/mtor pathway[J]. Oncol Rep, 2015, 33(6):3085-3092.
[14]
CHENG H, SHCHERBA M, PENDURTI G, et al. Targeting the pi3k/akt/mtor pathway: potential for lung cancer treatment[J]. Lung Cancer Manag, 2014, 3(1):67-75.
[15]
PENG Y, LI L, HUANG M, et al. Angiogenin interacts with ribonuclease inhibitor regulating pi3k/akt/mtor signaling pathway in bladder cancer cells[J]. Cell Signal, 2014, 26(12):2782-2792.
[16]
BAEK S H, KO J H, LEE J H, et al. Ginkgolic acid inhibits invasion and migration and tgf-beta-induced emt of lung cancer cells through pi3k/akt/mtor inactivation[J]. J Cell Physiol, 2017, 232(2):346-354.
[17]
BLANCO E, SANGAI T, WU S, et al. Colocalized delivery of rapamycin and paclitaxel to tumors enhances synergistic targeting of the pi3k/akt/mtor pathway[J]. Mol Ther, 2014, 22(7):1310-1319.
[18]
BAI H, LI H, LI W, et al. The pi3k/akt/mtor pathway is a potential predictor of distinct invasive and migratory capacities in human ovarian cancer cell lines[J]. Oncotarget, 2015, 6(28):25520-25532.
[19]
CAI Y, TAN X, LIU J, et al. Inhibition of pi3k/akt/mtor signaling pathway enhances the sensitivity of the skov3/ddp ovarian cancer cell line to cisplatin in vitro[J]. Chin J Cancer Res(�й���֢�о�), 2014, 26(5):564-572.
[20]
BANG Y J, IM S A, LEE K W, et al. Randomized, double-blind phase ii trial with prospective classification by atm protein level to evaluate the efficacy and tolerability of olaparib plus paclitaxel in patients with recurrent or metastatic gastric cancer[J]. J Clin Oncol, 2015, 33(33):3858-3865.
[21]
CHEDGY E C, BLACK P C. Moving beyond the androgen receptor in advanced prostate cancer commentary on: DNA-repair defects and olaparib in metastatic prostate cancer[J]. Urology, 2016, 8910-11.
[22]
VAN DER NOLL R, MARCHETTI S, STEEGHS N, et al. Long-term safety and anti-tumour activity of olaparib monotherapy after combination with carboplatin and paclitaxel in patients with advanced breast, ovarian or fallopian tube cancer[J]. Br J Cancer, 2015, 113(3):396-402.