## 4 Discussion  
Gefitinib is a representative EGFR inhibitor and oral anticancer drug that is frequently used to treat various malignancies, including lung and breast cancers, and is known to mainly inhibit the EGFR tyrosine kinase domain. As a target-oriented anticancer agent, gefitinib is also known to have much lower toxicity than conventional cytotoxic anticancer agents [31; 32]. However, the drug has been reported to cause various unintended side effects, including skin rashes, diarrhea, nausea, vomiting, anorexia, gastritis, dehydration, paronychia, liver toxicity, asthenia, conjunctivitis, plepharitis, interstitial lung disease,  
Figure 15: Representative histological profiles of the periovarian fat pads taken from intact or NCI-H520 tumor cell xenograft mice. (**A**) = Intact control; (**B**) = tumor-bearing control; (**C**) = gefitinib 120 mg/kg; (**D**) = SKOG 400 mg/kg; (**E**) = Gefitinib 120 mg/kg and SKOG 400 mg/kg; (**F**) = Gefitinib 120 mg/kg and SKOG 200 mg/kg; (**G**) = gefitinib 120 mg/kg and SKOG 100 mg/kg. AR = Adenophorae Radix; KOG = _Kyounggokgo_; SKOG = _sasam-Kyeonggoko_. All Hematoxylin-Eosin-stained. Scale bars = 100 μm. \begin{table}
\begin{tabular}{c c c} \hline \hline
**Groups** & **Total Thickness** & **White Adipocyte Diameters** \\  & **(mm/Central Regions)** & **(\(\mu\)m)** \\ \hline Single-formula-treated & & \\ \begin{tabular}{c} Gefitinib \\ SKOG \\ \end{tabular} & \begin{tabular}{c} 375.75 \(\pm\) 91.45 a \\ 650.00 \(\pm\) 121.29 abc \\ \end{tabular} & \begin{tabular}{c} 12.36 \(\pm\) 1.95 d \\ 21.85 \(\pm\) 3.14 def \\ \end{tabular} \\ \begin{tabular}{c} Gefitinib \\ \end{tabular} & \begin{tabular}{c} 400 mg/kg \\ 200 mg/kg \\ 100 mg/kg \\ \end{tabular} & \
\begin{tabular}{c} 1453.00 \(\pm\) 192.34 abc \\ 1096.00 \(\pm\) 128.90 abc \\ 965.00 \(\pm\) 192.82 abc \\ \end{tabular} &
\begin{tabular}{c} 37.95 \(\pm\) 10.89 def \\ 32.51 \(\pm\) 11.42 def \\ 25.10 \(\pm\) 6.62 def \\ \end{tabular} \\ \hline \hline \end{tabular}  
* TB = tumor-bearing; AR = Adenophorae Radix; KOG = _Kyounggokgo_; SKOG = _sasam-Kyeonggoko_. \({}^{a}\)_p_ \(<\) 0.01 versus intact control, assessed by the least significant difference (LSD) multi-comparison test; \({}^{b}\)_p_ \(<\) 0.01 versus TB control assessed by the least significant difference (LSD) multi-comparison test; \({}^{c}\)_p_ \(<\) 0.01 versus gefitinib-single-formula-treated rodents, assessed by the least significant difference (LSD) multi-comparison test; \({}^{d}\)_p_ \(<\) 0.01 versus intact control, assessed by the Mann–Whitney U test; \({}^{e}\)_p_ \(<\) 0.01 versus TB control, assessed by the Mann–Whitney U test; \({}^{f}\)_p_ \(<\) 0.01 versus gefitinib-single-formula-treated rodents, assessed by the Mann–Whitney U test.  
\end{table} 
Table 9: _Cont._corneal erosion, and eyelash loss [1; 2]. Hypersensitivity to gefitinib has also been reported [33; 34]. Other studies have suggested that the drug causes liver toxicity due to the increase in lipid peroxidation due to metabolites formed in the liver and damage to the antioxidant defense system [35]. With the recent emergence of resistant malignant tumor cells due to mutations of EGFR [36; 37], attempts have been made to solve the toxicity and tolerance problems associated with gefitinib through the co-administration of natural products and drugs, including various antioxidants [38; 39]. Sasam-Kyeongokgo is a mixed prescription of Kyeongokgo, a typical complex prescription that has traditionally been taken for health promotion in Korea [10; 11], and sasam, which has been utilized for the treatment of various respiratory diseases [3; 5]. In this study, as part of the effort to develop new effective anticancer therapies for lung cancer patients, the effects of sasam-Kyeongokgo on the anticancer activity of gefitinib were investigated in the NCI-H520 cell line, a representative squamous cell carcinoma non-small-cell lung cancer cell line showing gefitinib resistance [40; 41]. Cytotoxicity evaluation involves the assessment of a candidate substance's toxicity to cells.