Dynamic characterization of drug resistance and heterogeneity of the gastric cancer cell BGC823 using single-cell Raman spectroscopy

Abstract

Drug resistance and heterogeneous characteristics of human gastric carcinoma cells (BGC823) under the treatment of paclitaxel (PTX) were investigated using single-cell Raman spectroscopy (RS). RS of normal and drug-resistant BGC823 cells (DR-BGC823) were collected and analyzed using arithmetic, statistic and individual spectrum analysis. The dynamic effects of paclitaxel (PTX) in normal and DR-BGC823 cells were evaluated dynamically. The RS intensity changed with PTX over time and produced distinct different results for the two types of cells. The average RS intensities of the normal BGC823 cells initially decreased and then increased under PTX treatment after 24 hours. In contrast, upon exposure to PTX, the average intensity of the DR-BGC823 cells initially increased within 12 hours and then gradually decreased and approached a steady state. The temporal variation of the typical component in the cells was analyzed by comparing the ratios between Raman bands. More importantly, the heterogeneous characteristics of the BGC823 cells under PTX treatment were quantified and clustered using hierarchical trees combined with RS intensity changes. The 'outlier' cells related to drug resistance were discriminated. The heterogeneity of the normal BGC823 cells under drug treatment gradually appeared over time, and was evaluated with the eigenvalues of principal component analysis (PCA). Our study indicates that single-cell RS may be useful in systematically and dynamically characterizing the drug response of cancer cells at the single-cell level.

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

“…In the 40 T group, the extended incubation period resulted in an increase in the protein peak intensities at 757, 883, 941, 1001, 1127, 1172, 1519, 1612 cm −1 , which is consistent with increased production of anti‐apoptotic proteins to counteract DAPT effects and inhibit apoptosis [54, 55]. Thus, for cells treated with the same DAPT dose, the long‐term cytostatic effects might be better than cells treated for shorter periods, indicating that cell resistance may be the main reason for long‐term treatment [56].…”

Confocal Raman Spectral Imaging Study of DAPT, a γ-secretase Inhibitor, Induced Physiological and Biochemical Reponses in Osteosarcoma Cells

“…The sharp band at 1001 cm -1 corresponds to the symmetric circular breathing pattern of phenylalanine and is very sensitive to cell death. This peak can also be used to determine the kinetics of cell apoptosis [46].…”

Sub-cellular dynamic investigation of the multi-component drug on the gastric cancer cell BGC823 using Raman spectroscopy

“…All the RS was normalized by area. As our previous work showed 16 , the area under the RS curve is a more suitable and accurate index.…”

“…Micro-Raman spectroscopy (RS), known as molecular fingerprint spectroscopy, is a label-free and noninvasive technique to characterize the chemicals component and content in cell samples 13,14 . The application of RS in drug screening and investigation of cell response profiles has been explored in many anticancer drugs such as cisplatin (an alkylating and DNA binding agent), doxorubicin, vincristine, paclitaxel ect [15][16][17][18] . Some of the studies even explored the study of the anticancer drug at the subcellular level 15,[19][20][21] .…”