Ropivacaine inhibits proliferation and invasion and promotes apoptosis and autophagy in bladder cancer cells via inhibiting PI3K/AKT pathway

被引:10
作者
Qiao, Hui [1 ]
Zhang, Wei [2 ]
Liu, Pengfei [1 ]
Zhu, Ruilou [2 ]
Zhang, Jing [1 ]
Gao, Jing [1 ]
Li, Tianzuo [1 ]
Zhang, Jiaqiang [2 ]
机构
[1] Capital Med Univ, Beijing Shijitan Hosp, Dept Anesthesiol, Beijing, Peoples R China
[2] Zhengzhou Univ, Henan Prov Peoples Hosp, Dept Anesthesiol & Perioperat Med, Peoples Hosp, 7 Weiwu Rd, Zhengzhou 450003, Henan, Peoples R China
关键词
apoptosis; autophagy; bladder cancer; local anesthetics; PI3K; AKT signal pathway;
D O I
10.1002/jbt.23233
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Application of a certain concentration of local anesthetics during tumor resection inhibits the progression of tumor. The effects of ropivacaine in bladder cancer (BC) have never been explored. We explored the effects of ropivacaine on the progression of BC in vitro and in vivo. CCK8 assay and EDU staining was conducted to examine cell proliferation. Flow cytometry and transwell assay were performed to evaluate apoptosis and invasion, respectively. Expression of light chain 3 (LC3) was observed through immunofluorescence. Furthermore, the xenograft tumor model of BC was built to detect the effects of ropivacaine in vivo. IHC and TUNEL assay were conducted to detect cell proliferation and apoptosis in vivo. Ropivacaine inhibited the proliferation of T24 and 5639 cells with the 50% inhibitory concentration (IC50) of 20.08 and 31.86 mu M, respectively. Ropivacaine suppressed the invasion ability and induces the apoptosis of cells. Besides, ropivacaine triggers obvious autophagy in BC cells. Moreover, ropivacaine blocks the PI3K/AKT signal pathway in BC cells. The impact of ropivacaine on cell viability, motility, and autophagy was reversed by 740 Y-P, the activator of PI3K/AKT signal pathway. The in vivo experiments demonstrated that ropivacaine inhibited the proliferation and mobility of BC. Ropivacaine has anti-carcinoma effects in BC via inactivating PI3K/AKT pathway, providing a new theoretical reference for the use of local anesthetics in the treatment of BC.
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页数:11
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共 42 条
  • [1] Local anaesthetic use in cancer surgery and disease recurrence: role of voltage-gated sodium channels? (vol 113, pg 899, 2015)
    Fraser, S. P.
    Foo, I.
    Djamgoz, M. B. A.
    [J]. BRITISH JOURNAL OF ANAESTHESIA, 2015, 114 (06) : 1014 - 1014
  • [2] Pharmacological inhibition of autophagy by 3-MA attenuates hyperuricemic nephropathy
    Bao, Jinfang
    Shi, Yingfeng
    Tao, Min
    Liu, Na
    Zhuang, Shougang
    Yuan, Weijie
    [J]. CLINICAL SCIENCE, 2018, 132 (21) : 2299 - 2322
  • [3] Bennett Mike, 2017, Am Soc Clin Oncol Educ Book, V37, P705, DOI 10.14694/EDBK_180469
  • [4] Anesthetics impact on cancer recurrence: What do we know
    Bharati, Sachidanand Jee
    Chowdhury, Tumul
    Bergese, Sergio D.
    Ghosh, Subhamay
    [J]. JOURNAL OF CANCER RESEARCH AND THERAPEUTICS, 2016, 12 (02) : 464 - 468
  • [5] Autophagy modulation: a prudent approach in cancer treatment?
    Bishop, Eleanor
    Bradshaw, Tracey D.
    [J]. CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2018, 82 (06) : 913 - 922
  • [6] Therapeutic Targeting of Autophagy in Disease: Biology and Pharmacology
    Cheng, Yan
    Ren, Xingcong
    Hait, William N.
    Yang, Jin-Ming
    [J]. PHARMACOLOGICAL REVIEWS, 2013, 65 (04) : 1162 - 1197
  • [7] Anaesthesia for oncological surgery - can it really influence cancer recurrence?
    Ciechanowicz, S. J.
    Ma, D.
    [J]. ANAESTHESIA, 2016, 71 (02) : 127 - 131
  • [8] VEGFA and tumour angiogenesis
    Claesson-Welsh, L.
    Welsh, M.
    [J]. JOURNAL OF INTERNAL MEDICINE, 2013, 273 (02) : 114 - 127
  • [9] Microenvironmental regulation of tumour angiogenesis
    de Palma, Michele
    Biziato, Daniela
    Petrova, Tatiana V.
    [J]. NATURE REVIEWS CANCER, 2017, 17 (08) : 457 - 474
  • [10] Cross talk between apoptosis and autophagy by caspase-mediated cleavage of Beclin 1
    Djavaheri-Mergny, M.
    Maiuri, M. C.
    Kroemer, G.
    [J]. ONCOGENE, 2010, 29 (12) : 1717 - 1719