Zdravkovic Bogdan, Zdravkovic Tanja Prunk, Zdravkovic Marko, Strukelj Borut, Ferk Polonca
University Medical Centre Maribor, Maribor, Slovenia.
J BUON. 2019 Jan-Feb;24(1):338-346.
There is no clear evidence on whether sunscreens and personal care products containing UV-filters like titanium dioxide (TiO2) are protective against or may be a contributing factor in melanoma development. Extensive studies have shown that TiO2 can cause cell toxicity under in vitro and in vivo conditions. The transmembrane protein ABCB5 is closely linked to tumorigenicity, progression and disease recurrence of diverse human malignancies, including melanoma. Accordingly, the aim of the present study was to investigate in vitro any potential influence of nanosized TiO2 (nano-TiO2) on metastatic melanoma cells' metabolic activity, cytotoxicity and ABCB5 mRNA expression.
The human metastatic melanoma cell line WM-266-4 (ATCC) was used to obtain dose- and time-dependent responses. We used the MTT and LDH assays to measure metabolic activity of selected cells and cytotoxicity. Real-time quantitative PCR (RT-qPCR) was performed and gene expression ratios were calculated for the target (ABCB5) and the reference (LDHA) gene. Standard statistical tests were used for analysis in SPSS and Excell.
Our results suggest decreased metastatic melanoma cells' metabolic activity, increased cytotoxicity and increased ABCB5 mRNA expression after 24 and 48 hrs as compared to control (untreated) cells (p<0.05). Thus, we showed that nano-TiO2 might influence cells' invasiveness and aggressiveness.
We show for the first time that ABCB5 expression in metastatic melanoma cells might be affected by nano-TiO2 exposure. In addition, nano-TiO2 as a sunscreen ingredient might play a role in metastatic melanoma progression.
对于含有紫外线过滤剂（如二氧化钛（TiO₂））的防晒霜和个人护理产品是否具有防护作用或可能是黑色素瘤发展的一个促成因素，目前尚无明确证据。大量研究表明，TiO₂在体外和体内条件下均可导致细胞毒性。跨膜蛋白ABCB5与包括黑色素瘤在内的多种人类恶性肿瘤的致瘤性、进展及疾病复发密切相关。因此，本研究的目的是在体外研究纳米二氧化钛（纳米TiO₂）对转移性黑色素瘤细胞代谢活性、细胞毒性及ABCB5 mRNA表达的任何潜在影响。
使用人转移性黑色素瘤细胞系WM - 266 - 4（美国典型培养物保藏中心）来获得剂量和时间依赖性反应。我们使用MTT和LDH测定法来测量所选细胞的代谢活性和细胞毒性。进行实时定量PCR（RT - qPCR），并计算靶基因（ABCB5）和参照基因（LDHA）的基因表达比率。使用标准统计测试在SPSS和Excel中进行分析。
我们的结果表明，与对照（未处理）细胞相比，24小时和48小时后转移性黑色素瘤细胞的代谢活性降低、细胞毒性增加且ABCB5 mRNA表达增加（p<0.05）。因此，我们表明纳米TiO₂可能影响细胞的侵袭性和攻击性。
我们首次表明，纳米TiO₂暴露可能会影响转移性黑色素瘤细胞中ABCB5的表达。此外，纳米TiO₂作为一种防晒成分可能在转移性黑色素瘤进展中起作用。
