The absence of confirmed signal in dark matter (DM) direct detection (DD) may suggest weak interactions of DM with gluons and light quarks. In this work we consider a real scalar dark matter $S$ interacting dominantly with $U_i=c_R,t_R$ via a vector-like fermion $\psi$ and new couplings $y_i$ with $i=2,3$ being flavor index. DM-nucleon scattering proceed through both Higgs portal (HP) and vector-like portal (VLP), in which HP can receive sizable radiative corrections from VLP. DM-heavy quark ($c_R,t_R$) interactions generate DM-gluon scattering via loop, in which we include renormalization group equation and heavy quark threshold effects. For $y_3=0.5, y_2=0.5, 1, 3$, DM relic abundance, XENON1T, Fermi-LAT and 13 TeV LHC data can exclude most of $m_S<m_t/2$. FCNC of top quark exist at both tree and loop level and the branch ratios are typically below $10^{-7}$ and safe from the current measurements.