Table 2.

Methodology for the in vitro development of MAP resistant models in OS.

	Dose response exposure time (h)	EC50 (µM)	Cell line	Model exposure method (–h)	Starting conc. (µM)	Final conc. (µM)	RI	Variants	Reference	Model
MTX	24	25.78	SAOS2	P-24	1.1	4.4	12.7	NS	[49]	Wang_SAOS2/MTX-P
	48	0.35	MG63	P-48	0.22	22	112.4	NS	[69]	Xu_MG63/MTX-P
		0.47	U2OS				93.1			Xu_U2OS/MTX-P
	96	0.03	SAOS2	C	0.0066	0.066–2.2	15–281	Y	[34, 36, 37]	Serra_SAOS2/MTX-C
		0.01	U2OS			0.0066–2.2	3c–135			Serra_U2OS/MTX-C
DOX	3	0.4	143b	P-3	NS	100	187.5	NS	[43]	Rajkumar_143B/DOX-P
	NS	0.14	U2OS	P-24	0.345	NS	95.6	NS	[44]	Shen_U2OS/DOX-P
		0.18	MG63				72.9			Shen_MG63/DOX-P
	48	1.8	HOS	C	0.01	1	11.28	NS	[52]	Cheng_HOS/DOX-C
		2.1	MG63				12.8			Cheng_MG63/DOX-C
	96	0.013	SAOS2	C	0.0052	0.0517–1	72–338	Y	[34, 64, 97]	Serra_SAOS2/DOX-C
		0.01	U2OS				15–330			Serra_U2OS/DOX-C
	48	1.6	KHOS	C	0.0035	0.035	6.3	NS	[50, 51, 59, 61, 71, 72, 120]	Lourda_KHOS/DOX-C
		10.78	U2OS				15			Lourda_U2OS/DOX-C
	48	11.15	MG63	C	1	10	4.5c	NS	[47]	Ma_MG63/DOX-C
	72	0.035	MG63	C	0.0517	0.0517–0.1724	10–28	Y	[35]	Roncuzzi_MG63/DOX-C
	48	1.1	MG63	C	0.0043	1.724	10.5	NS	[58]	Wang_MG63/DOX-C
	NS	5.52	MG63	C	0.01	0.1	6c	NS	[65]	Xu_MG63/DOX-C
	72	0.006	MG63	C	0.005	0.065	18.2	NS	[42]	Zhang_MG63/DOX-C
	24a	1.15	U2OS	C	0.015	0.12	3c	NS	[48]	Shu_U2OS/DOX-C
		0.93	HOS				3.5c			Shu_HOS/DOX-C
	NS	2.01	KHOS	C	NS	NS	5.6c	NS	[62]	Guan_KHOS/DOX-C
		4.33	MG63				6.9			Guan_MG63/DOX-C
	24	0.03	U2OS	C	NS	NS	30.7	NS	[57]	Sugiu_U2OS/DOX-C
		0.025	MG63				19.2			Sugiu_MG63/DOX-C
	48	0.226	SAOS2	C	0.001	5	46.8	NS	[67]	Liu_SAOS2/DOX-C
	48	3.5	MG63	C	NS	NS	8	NS	[66]	Yuan_MG63/DOX-C
		3.5	KHOS				3.3c			Yuan_KHOS/DOX-C
	24	2.87	MG63	C	0.005	0.1	7.5	NS	[55]	Xia_MG63/DOX-C
CDDP	NS	1.8	SAOS2	P-72	1	50	4.44c	NS	[53]	Fan_SAOS2/CDDP-P
	72	8.17	SOSP-9607	P-48	0.333	6.66	6.3	NS	[54]	Han_SOSP9607/CDDP-P
	24	35	HOS	P-2	3333	3333	2.2c	NS	[41]	Mukherjee_HOS/CDDP-P
	24b	9	SAOS2	P-24	1.5	16	3.4c	NS	[56, 68, 70]	Song_SAOS2/CDDP-P
		10	MG63				3.2c			Song_MG63/CDDP-P
	NS	5	MG63	P-72	0.1	0.2	4c	NS	[73]	Zou_MG63/CDDP-P
	72	9.04	U2OS	C	10	10	14.1	NS	[46]	Jiang_U2OS/CDDP-C
		8.35	MG63				14.5			Jiang_MG63/CDDP-C
	72b	3.33	SAOS2	C	0.333	3.33	3c	NS	[63]	Li_SAOS2/CDDP-C
	48	0.85	MG63	C	0.5	2	6.1c	NS	[47]	Ma_MG63/CDDP-C
	NS	NS	SAOS	C	1	3.33	4c	NS	[60]	Zhao_SAOS2/CDDP-C
			U2OS				5c			Zhao_U2OS/CDDP-C

Data extracted from in vitro studies included in this review. The concentration that elicits a half maximal response (EC₅₀) is stated for the parental cell line. Resistance index (RI) indicates the fold resistance to chemotherapy.

P pulse, C continuous, NS not stated in paper.

^aPulsing strategy was used for the dose response experiment where cells were exposed for only 24 h of the total 72 h assay.

^bMultiple timepoints used for dose response experiments.

^cClinically relevant levels of resistance.