Teichoic acid differentially modulates TLR4 expression in sensitive and resistant to cisplatin

N. Senchylo, O. Gorbach, L. Dubovtseva, O. Skachkova, P. Yakovlev, T. Skaterna, L. Drobot, L. Garmanchuk
Taras Shevchenko National University of Kyiv, Kyiv; National Cancer Institute, Kyiv; National Cancer Institute, Kyiv; National Cancer Institute, Kyiv; Taras Shevchenko National University of Kyiv, Kyiv; Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine (NASU), Kyiv; Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine (NASU), Kyiv; Taras Shevchenko National University of Kyiv, Kyiv

Abstract


The Toll-like receptor family plays crucial role in the innate immune system, recognizing the molecular structures associated with pathogens derived from different microbes. TLRs also recognize the molecular structures associated with damage associated with certain diseases, such as cancer. They can either promote tumorigenesis, or suppress it. Besides, the promotion of the tumor cells growth may be associated with the acquisition of drug resistance. The data on the TLR4 expression level changes during this pathological process are controversial. That is why the purpose of our study was to determine the expression level of TLR4 in cisplatin-sensitive and cisplatin-resistant lung cancer cells. Cells line NCI-H69 (human small cell lung carcinoma) and a drug resistant subline of NCI-H69/CPR were used to determine the expression level of TLR4.Incubation of cells with teichoic acid (1 μg / ml) was performed under standard conditions for two days. The level of TLR4 expression in the cell was determined with RT-PCR at 7500 Real-Time PCR Systems ("Applied Bіosystems", USA) and specific primers and asymmetric cyan cationic fluorochrom SYBRGreen (С32Н37N4S+) with spike of consumption at λmax = 488 nm and fluorescence at λmax = 522 nm. It was shown that TLR4 expression level was almost two times lower in WT H69 cells compared with H69 cells resistant to cisplatin. In contrast,
teichoic acid oppositely influenced TLR4 expression level: increased by 1.3-times in WT H69 cells whereas decreased 4-times in H69 cells resistant to cisplatin compared with corresponding control samples without teichoic acid. In cisplatin-resistant lung cancer cells found high expression of TLR4 can be inhibited by addingteichoic acida ligand to TLRs.

Keywords


TLR4 expression, NCI-H69 and NCI-H69/CPR cisplatin-resistant cells line, teichoic acid

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Received: 07.10.2019

Revised: 08.11.2019

Signed for the press: 08.11.2019




DOI: http://dx.doi.org/10.17721/1728_2748.2019.79.90-94

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