# Photodynamic Therapy Effects on Oral Dysplastic Keratinocyte Cell Cultures: A Systematic Review
## 3 Results
Among the assessed analytes, Bcl-2, P70S6K kinase, Raf-1, and bad proteins represent the apoptosis-related biomolecules that showed expression variations with the greatest amplitude. In 2019, the work from [PERSON] et al. [28] reported the use of methyl aminolevulinate photodynamic therapy (MAL-PDT) as a prevention tool against the progression of pre-cancerous lesions to oral cancer. The study found that MAL-PDT induced autophagic cell death in DOX oral pre-cancerous cells and decreased tumor growth in hamster buccal pouch tumors induced by DMBA. The expression of autophagy marker p62/SQSTM1 was increased in DOX cells at 4 h after MAL-PDT treatment, but it was decreased in the pre-cancerous lesions of hamster buccal pouch at 2 weeks after MAL-PDT treatment, suggesting a time-dependent change in the expression of autophagy markers after MAL-PDT treatment. The effects of in vitro PDT on human oral pre-cancerous cell line (DOK) and an oral squamous cell carcinoma cell line (CAL-27) were also evaluated by [PERSON] et al. in 2020 [29] using 5-aminolevulinic acid-mediated photodynamic therapy. The study reported that ALA-PDT inhibited the proliferation of cell lines in a dose- and time-dependent manner. However, the susceptibilities of these cell lines to ALA-PDT were different. The rates of apoptosis were higher in CAL-27 cells than in DOX cells. The study also revealed changes in the expression of matrix metallopeptidase 2 (MMP-2) and MMP-9 after the treatment. Overall, the study suggested that ALA-PDT may be an effective treatment for oral cancer and pre-cancerous lesions. [PERSON] et al. [25] explored the same methodology (ALA-PDT) for the treatment of oral pre-cancerous cells. The study found that ALA-PDT can suppress the growth of oral pre-cancerous cells by regulating the transforming growth factor beta (TGF-\(\beta\)) signaling pathway. The study also found that the suppressive effect of ALA-PDT was enhanced when combined with the TGF-\(\beta\) receptor inhibitor LY2109761. An interesting paper by [PERSON] et al. [26] explored the potential of methylene blue (MB) as a photosensitizer for PDT in cell cultures of oral squamous cell carcinoma, oral leukoplakia, and immortalized keratinocytes. The study showed that MBPDT could significantly decrease the expression of matrix metalloproteinases (MMPs) in all involved cell lines; the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to confirm the efficacy of MB-PDT. Finally, in 2022, [PERSON] et al. [30] analyzed the development of a hydrogel patch called PACA that can be used to deliver ALA for the PDT of oral potentially malignant cells. The study found that PACA hydrogel-mediated PDT (PACA-PDT) improved OPMDs in vitro and in a hamster oral carcinogenesis model. The paper also reported the results of a trial involving 60 OPMD volunteers, which demonstrated the feasibility and comfort of the PACA hydrogel patch. \begin{table}
\begin{tabular}{c c c c c c c c c c c c c c c} \hline \hline
**Study** & **1** & **2** & **3** & **4** & **5** & **6** & **7** & **8** & **9** & **10** & **11** & **12** & **SCORE** & **Risk of Bias** \\ \hline [PERSON] et al. [24] (2012) & 2 & 0 & 2 & 2 & 2 & 0 & 0 & 2 & 2 & 0 & 2 & 2 & 66.7\% & Medium \\ [PERSON] et al. [25] (2022) & 2 & 2 & 2 & 2 & 0 & 2 & 2 & 2 & 0 & 2 & 2 & 83.3\% & Low \\ [PERSON] et al. [26] (2022) & 2 & 0 & 2 & 2 & 2 & 0 & 2 & 2 & 0 & 2 & 2 & 75.0\% & Low \\ [PERSON] et al. [27] (2014) & 2 & 0 & 2 & 2 & 2 & 0 & 2 & 2 & 0 & 2 & 2 & 75.0\% & Low \\ [PERSON] et al. [28] (2019) & 2 & 0 & 2 & 2 & 2 & 0 & 2 & 2 & 2 & 0 & 2 & 2 & 75.0\% & Low \\ [PERSON] et al. [29] (2020) & 2 & 0 & 2 & 2 & 2 & 0 & 0 & 2 & 2 & 0 & 2 & 2 & 66.7\% & Medium \\ [PERSON] et al. [30] (2022) & 2 & 0 & 2 & 2 & 2 & 0 & 0 & 2 & 2 & 0 & 2 & 2 & 66.7\% & Medium \\ \hline \hline \end{tabular}
\end{table} 
Table 2: QUIN Tool scores of in vitro studies. Scores for studies are achieved according to the following: adequately specified = 2; inadequately specified = 1; not specified = 0.