Unveiling dose- and time-dependent osteosarcoma cell responses to the γ-secretase inhibitor,DAPT, by confocal Raman microscopy

被引:8
作者
Li, Jie [1 ]
Qin, Jie [2 ]
Zeng, Haishan [3 ]
Li, Jing [2 ]
Wang, Kaige [1 ]
Wang, Shuang [1 ]
机构
[1] Northwest Univ, Inst Photon & Photon Technol, 229 North Taibai Rd, Xian 710069, Shaanxi, Peoples R China
[2] Xi An Jiao Tong Univ, Affiliated Hosp 2, Dept Orthoped, Xian, Shaanxi, Peoples R China
[3] BC Canc Res Ctr, Imaging Unit, Integrat Oncol Dept, Vancouver, BC, Canada
基金
中国国家自然科学基金;
关键词
confocal Raman micro-spectroscopy; DAPT; osteosarcoma cells; partial least squares-discriminant analysis; principal component analysis-linear discriminant analysis; PARTIAL LEAST-SQUARES; SPECTROSCOPY; APOPTOSIS; PATHWAY; SINGLE; BREAST; DAPT; DISCRIMINATION; CLASSIFICATION; PROLIFERATION;
D O I
10.1002/jbio.202000238
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Using confocal Raman micro-spectroscopy, this study aims to elucidate the cellular responses of the gamma-secretase inhibitor, N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), in osteosarcoma (OS) cells in a dose- and time-dependent manner. The K7M2 murine OS cell line was treated with different DAPT doses (0, 10, 20, and 40 mu M) for 24 and 48 hours before investigations. Significant compositional changes (nucleic acids, protein and lipid) after DAPT treatment were addressed, which testified inhibitory effect of DAPT on the growth of OS cells. Moreover, both partial least squares-discriminant analysis (PLS-DA) and principal component analysis-linear discriminant analysis (PCA-LDA) analyses revealed governing composition variations among groups by distinguishing their spectral characteristics. Furthermore, by adopting leave-one-out cross validation method, it is shown that PLS-DA exhibited more classification capacity than PCA-LDA algorithm. Hence, by understanding the DAPT-based cellular variations, the achieved results provided an experimental foundation to establish new DAPT-based anticancer therapeutic strategies, and preclinical Raman analytical methodologies on drug-cell interactions.
引用
收藏
页数:13
相关论文
共 58 条
[1]  
ARENDS MJ, 1990, AM J PATHOL, V136, P593
[2]   Partial least squares for discrimination [J].
Barker, M ;
Rayens, W .
JOURNAL OF CHEMOMETRICS, 2003, 17 (03) :166-173
[3]   Chemotherapeutic response to cisplatin-like drugs in human breast cancer cells probed by vibrational microspectroscopy [J].
Batista de Carvalho, A. L. M. ;
Pilling, M. ;
Gardner, P. ;
Doherty, J. ;
Cinque, G. ;
Wehbe, K. ;
Kelley, C. ;
Batista de Carvalho, L. A. E. ;
Marques, M. P. M. .
FARADAY DISCUSSIONS, 2016, 187 :273-298
[4]   Characterizing variability in in vivo Raman spectroscopic properties of different anatomical sites of normal tissue in the oral cavity [J].
Bergholt, Mads Sylvest ;
Zheng, Wei ;
Huang, Zhiwei .
JOURNAL OF RAMAN SPECTROSCOPY, 2012, 43 (02) :255-262
[5]   Notch pathway inhibition using DAPT, a γ-secretase inhibitor (GSI), enhances the antitumor effect of cisplatin in resistant osteosarcoma [J].
Dai, Guo ;
Deng, Shuang ;
Guo, Weichun ;
Yu, Ling ;
Yang, Jian ;
Zhou, Sheng ;
Gao, Tian .
MOLECULAR CARCINOGENESIS, 2019, 58 (01) :3-18
[6]   Discrimination between authentic and counterfeit banknotes using Raman spectroscopy and PLS-DA with uncertainty estimation [J].
de Almeida, Mariana R. ;
Correa, Deleon N. ;
Rocha, Werickson F. C. ;
Scafi, Francisco J. O. ;
Poppi, Ronei J. .
MICROCHEMICAL JOURNAL, 2013, 109 :170-177
[7]   Integrated fingerprint and high wavenumber confocal Raman spectroscopy for in vivo diagnosis of cervical precancer [J].
Duraipandian, Shiyamala ;
Zheng, Wei ;
Joseph Ng ;
Low, Jeffrey J. H. ;
Ilancheran, A. ;
Huang, Zhiwei .
ADVANCED BIOMEDICAL AND CLINICAL DIAGNOSTIC SYSTEMS XI, 2013, 8572
[8]   Raman micro spectroscopy for in vitro drug screening: subcellular localisation and interactions of doxorubicin [J].
Farhane, Z. ;
Bonnier, F. ;
Casey, A. ;
Byrne, H. J. .
ANALYST, 2015, 140 (12) :4212-4223
[9]   Doxorubicin kinetics and effects on lung cancer cell lines using in vitro Raman micro-spectroscopy: binding signatures, drug resistance and DNA repair [J].
Farhane, Zeineb ;
Bonnier, Franck ;
Howe, Orla ;
Casey, Alan ;
Byrne, Hugh J. .
JOURNAL OF BIOPHOTONICS, 2018, 11 (01)
[10]   An in vitro study of the interaction of the chemotherapeutic drug Actinomycin D with lung cancer cell lines using Raman micro-spectroscopy [J].
Farhane, Zeineb ;
Bonnier, Franck ;
Byrne, Hugh J. .
JOURNAL OF BIOPHOTONICS, 2018, 11 (01)